KdpC is a periplasmic, single-pass membrane subunit of the KdpFABC high-affinity potassium-transporting ATPase complex. It functions as a catalytic chaperone that increases the ATP-binding affinity of the ATPase subunit KdpB by forming a transient KdpB/KdpC/ATP ternary complex. KdpC does not itself possess catalytic ATPase or hydrolase activity; rather, it modulates ion access in the periplasmic vestibule and stabilizes complex assembly. The KdpFABC complex is induced under potassium limitation to enable high-affinity K+ uptake (Stock et al., 2023).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0071805
potassium ion transmembrane transport
|
IEA
GO_REF:0000118 |
ACCEPT |
Summary: KdpC is part of the KdpFABC complex which transports potassium ions across the membrane. While KdpC does not directly catalyze ion transport (this is performed by KdpA/KdpB), it is an essential accessory subunit required for complex function. The annotation correctly reflects KdpC's involvement in the biological process.
Reason: KdpC is an essential subunit of the KdpFABC potassium-transporting ATPase. Contemporary structural and mechanistic studies confirm that KdpC is required for proper complex function, even though it does not directly catalyze transport. The 'involved_in' qualifier is appropriate for an accessory subunit that enables the process through its catalytic chaperone function.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
KdpC subunit role/definition: KdpC is periplasmically oriented and single-pass. Contemporary models assign KdpC a non-catalytic but essential structural/modulatory role
|
|
GO:0000166
nucleotide binding
|
IEA
GO_REF:0000043 |
REMOVE |
Summary: This annotation is based on UniProtKB keyword mapping (KW-0547). The annotation is misleading for KdpC. While KdpC participates in forming a transient ternary complex with KdpB and ATP, it is KdpB that directly binds ATP. KdpC functions as a catalytic chaperone to increase ATP-binding affinity of KdpB, but does not itself possess intrinsic nucleotide-binding capability.
Reason: KdpC does not directly bind nucleotides. The UniProt HAMAP annotation states that KdpC "increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex." This describes an indirect role in modulating ATP binding to KdpB, not direct nucleotide binding by KdpC itself. The cryo-EM structures show ADP and Mg2+ bound in the KdpB N-domain, not KdpC. This is an over-annotation resulting from keyword propagation that does not accurately reflect KdpC's molecular function.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex
|
|
GO:0005524
ATP binding
|
IEA
GO_REF:0000120 |
REMOVE |
Summary: This annotation derives from UniRule:UR000058586 and keyword mapping. Like the nucleotide binding annotation, this is an over-annotation. KdpC participates in ternary complex formation with KdpB and ATP, but does not itself directly bind ATP. The ATP-binding site resides in KdpB, not KdpC.
Reason: KdpC is not an ATP-binding protein. The catalytic aspartate (D307) that becomes phosphorylated during the reaction cycle is located in KdpB, and ATP/ADP are bound to the KdpB N-domain. KdpC's role is to enhance ATP-binding affinity of KdpB through allosteric/chaperone mechanisms, not to directly bind ATP. This annotation incorrectly attributes to KdpC a molecular function that belongs to KdpB.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
KdpB is the P-type ATPase motor
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
D307 phosphorylated and ADP + two Mg2+ bound in the N-domain
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: KdpC is localized to the bacterial inner membrane (equivalent to plasma membrane) as a single-pass membrane protein with periplasmic orientation. This annotation is correct and well-supported.
Reason: Multiple sources confirm KdpC is a membrane protein. UniProt HAMAP annotation states "Cell inner membrane; Single-pass membrane protein." Structural studies confirm KdpC is periplasmically oriented and embedded in the cytoplasmic membrane. For bacteria, the inner/cytoplasmic membrane corresponds to GO:0005886 plasma membrane.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
Cell inner membrane
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
Periplasmically oriented, single-pass membrane protein embedded with KdpA/KdpB/KdpF in the cytoplasmic membrane
|
|
GO:0006811
monoatomic ion transport
|
IEA
GO_REF:0000043 |
MARK AS OVER ANNOTATED |
Summary: This annotation is too general. KdpC is specifically involved in potassium ion transport as part of the KdpFABC complex. The more specific term GO:0006813 (potassium ion transport) is already annotated.
Reason: While technically correct (potassium is a monoatomic ion), this annotation adds no information beyond what GO:0006813 (potassium ion transport) and GO:0071805 (potassium ion transmembrane transport) already provide. The KdpFABC complex is specifically a potassium transporter, not a general ion transporter. Retaining this broader term alongside the specific terms is redundant. However, this is not incorrect per se - just uninformative.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump induced under K+ limitation/osmotic stress
|
|
GO:0006813
potassium ion transport
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: KdpC is an essential subunit of the KdpFABC high-affinity potassium transport system. This biological process annotation is appropriate.
Reason: KdpC is required for proper function of the KdpFABC complex, which mediates high-affinity K+ uptake. The annotation correctly captures KdpC's involvement in the biological process of potassium ion transport. However, GO:0071805 (potassium ion transmembrane transport) is more specific and also present, so this annotation is somewhat redundant but not incorrect.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
Part of the high-affinity ATP-driven potassium transport (or Kdp) system
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
KdpFABC mediates high-affinity K+ uptake under limitation
|
|
GO:0008556
P-type potassium transmembrane transporter activity
|
IEA
GO_REF:0000120 |
MODIFY |
Summary: This molecular function annotation is inappropriate for KdpC. GO:0008556 describes the enzymatic transporter activity, which in the KdpFABC complex is performed by KdpB (the P-type ATPase) together with KdpA (the K+ channel). KdpC does not possess transporter activity; it is an accessory subunit with a regulatory/chaperone role.
Reason: GO:0008556 is defined as "Enables the transfer of a solute... according to the reaction: ATP + H2O + K+(out) = ADP + phosphate + K+(in)." This describes catalytic activity that KdpC does not possess. KdpB is the ATPase that hydrolyzes ATP (containing the catalytic aspartate D307), and KdpA is the K+ translocase. KdpC functions as a "catalytic chaperone" that modulates KdpB activity but does not itself catalyze transport. This annotation incorrectly attributes complex activity to an individual subunit that lacks the catalytic machinery.
Proposed replacements:
ATPase activator activity
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: This general membrane annotation is correct but redundant given the more specific GO:0005886 (plasma membrane) annotation already present.
Reason: KdpC is indeed a membrane protein, so this annotation is not incorrect. However, GO:0005886 (plasma membrane) is more specific and accurately describes KdpC's localization. This broader term adds no additional information. It derives from InterPro domain IPR003820 which appropriately associates KdpC with membranes.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
Single-pass membrane protein
|
|
GO:0016787
hydrolase activity
|
IEA
GO_REF:0000043 |
REMOVE |
Summary: This annotation is incorrect for KdpC. The hydrolase (ATPase) activity in the KdpFABC complex resides in KdpB, not KdpC. KdpC does not possess catalytic hydrolase activity.
Reason: The ATPase activity (ATP hydrolysis) is carried out by KdpB, which contains the catalytic aspartate D307 that becomes phosphorylated during the P-type ATPase cycle. KdpC has no catalytic residues and functions as a regulatory/ chaperone subunit. The UniProtKB keyword "Hydrolase" (KW-0378) was incorrectly propagated to KdpC, likely because the KdpFABC complex has hydrolase activity. This conflates complex function with individual subunit function. KdpC "acts as a catalytic chaperone" but is not itself a catalyst.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
catalytic aspartate D307 cycles through phosphorylation
file:DESVH/Q725T8/Q725T8-uniprot.txt
This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB
|
|
GO:0031004
potassium ion-transporting ATPase complex
|
ISS
GO_REF:0000024 |
NEW |
Summary: KdpC is part of the KdpFABC potassium ion-transporting ATPase complex. GO:0031004 specifically describes this complex in E. coli, noting that "KdpC and KdpF seem to be involved in assembly and stabilization of the complex."
Reason: This cellular component term precisely describes KdpC's localization as part of a defined protein complex. The GO term definition explicitly mentions KdpC: "The E. coli complex consists of 4 proteins: KdpA is the potassium ion translocase, KdpB is the ATPase, and KdpC and KdpF seem to be involved in assembly and stabilization of the complex." This is more informative than the generic membrane terms currently annotated.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
The system is composed of three essential subunits: KdpA, KdpB and KdpC
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump
|
|
GO:0001671
ATPase activator activity
|
ISS
GO_REF:0000024 |
NEW |
Summary: KdpC functions as a catalytic chaperone that increases ATP-binding affinity and promotes ATPase activity of KdpB. GO:0001671 ("Binds to and increases the activity of an ATP hydrolysis activity") accurately describes this molecular function.
Reason: This molecular function term accurately captures KdpC's primary role in the KdpFABC complex. Unlike the incorrect annotations of ATP binding or hydrolase activity, this term describes KdpC's actual regulatory function of enhancing KdpB's ATPase activity through formation of a transient ternary complex. This is supported by UniProt HAMAP annotation and contemporary structural studies.
Supporting Evidence:
file:DESVH/Q725T8/Q725T8-uniprot.txt
This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex
file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface
|
Q: Does KdpC directly contact ATP in the ternary complex, or does it act purely through allosteric effects on KdpB?
Q: Is there structural data specific to D. vulgaris KdpFABC that would confirm conservation of KdpC's role?
Experiment: Cryo-EM structure of KdpFABC with focus on KdpC-ATP proximity to determine if KdpC directly contacts ATP in the ternary complex.
Hypothesis: KdpC may directly contact ATP to facilitate its binding to KdpB
Experiment: KdpC mutagenesis affecting KdpB ATPase activity to identify KdpC residues critical for its catalytic chaperone function.
Hypothesis: Specific KdpC residues at the KdpB interface are required for ATPase activation
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template_file: templates/gene_research_go_focused.md
template_variables:
organism: DESVH
gene_id: Q725T8
gene_symbol: kdpC
uniprot_accession: Q725T8
protein_description: 'RecName: Full=Potassium-transporting ATPase KdpC subunit {ECO:0000256|HAMAP-Rule:MF_00276};
AltName: Full=ATP phosphohydrolase [potassium-transporting] C chain {ECO:0000256|HAMAP-Rule:MF_00276};
AltName: Full=Potassium-binding and translocating subunit C {ECO:0000256|HAMAP-Rule:MF_00276};
AltName: Full=Potassium-translocating ATPase C chain {ECO:0000256|HAMAP-Rule:MF_00276};'
gene_info: Name=kdpC {ECO:0000256|HAMAP-Rule:MF_00276, ECO:0000313|EMBL:AAS97805.1};
OrderedLocusNames=DVU_3337 {ECO:0000313|EMBL:AAS97805.1};
organism_full: Nitratidesulfovibrio vulgaris (strain ATCC 29579 / DSM 644 / CCUG
34227 / NCIMB 8303 / VKM B-1760 / Hildenborough) (Desulfovibrio vulgaris).
protein_family: Belongs to the KdpC family. {ECO:0000256|HAMAP-
protein_domains: KdpC. (IPR003820); KdpC (PF02669)
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citation_count: 18
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'kdpC' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene kdpC (gene ID: Q725T8, UniProt: Q725T8) in DESVH.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'kdpC' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene kdpC (gene ID: Q725T8, UniProt: Q725T8) in DESVH.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Plan overview
We verified the target identity and then synthesized recent primary/review literature on the bacterial KdpFABC K+ pump with emphasis on the KdpC subunit and late-breaking regulatory/structural insights (2023–2025). Organism-specific inferences to Desulfovibrio vulgaris Hildenborough (DVU_3337; UniProt Q725T8) are provided with caution due to limited species-specific primary data in the retrieved corpus.
Mandatory identity verification
- Gene symbol and product: The target is kdpC, encoding the KdpC subunit of the potassium-transporting ATPase (KdpFABC). This matches the UniProt description and canonical nomenclature for the KdpFABC complex. The KdpC subunit is a small, periplasmically oriented, single-pass membrane protein belonging to the KdpC family (PF02669; IPR003820), consistent with current structural/functional overviews of KdpFABC. (stock2023fastforwardonptype pages 4-6)
- Organism: Nitratidesulfovibrio (Desulfovibrio) vulgaris Hildenborough; locus DVU_3337 as provided. No contradictions were found in the contemporary KdpFABC literature surveyed; species-specific functional inference is based on conservation of the KdpC family and the architecture of KdpFABC. (stock2023fastforwardonptype pages 4-6)
1) Key concepts and current definitions
- The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump induced under K+ limitation/osmotic stress. KdpA provides K+ selectivity (Trk/Ktr/Kdp superfamily-like), KdpB is the P-type ATPase motor, KdpC is a periplasmic single-pass membrane subunit, and KdpF is a small membrane anchor. Central mechanistic concept: K+ moves via an intersubunit tunnel from the KdpA selectivity filter to the canonical ion-binding site in KdpB (CBS), coupling to the P-type ATPase Post–Albers-like cycle in KdpB. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
- KdpC subunit role/definition: KdpC is periplasmically oriented and single-pass. Contemporary models assign KdpC a non-catalytic but essential structural/modulatory role—controlling ion access to KdpA and stabilizing KdpFABC assembly. Its precise catalytic involvement remains limited; most catalytic chemistry resides in KdpB. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
2) Recent developments (2023–2024 priority; 2025 preprint where pertinent)
- High-resolution cryo-EM under turnover: A 2.1 Å structure of E. coli KdpFABC in an E1~P·ADP conformation shows strong K+ densities in KdpA’s selectivity filter and at KdpB’s CBS, with D307 phosphorylated and ADP + two Mg2+ bound in the N-domain, directly supporting the intersubunit-tunnel conduction and P-type coupling mechanism. URL: https://doi.org/10.1101/2025.05.05.652293 (May 2025). (hussein2025conductionpathwayfor pages 1-4)
- Intersubunit tunnel confirmation and mutagenesis: Functional assays and targeted mutations along the tunnel validate conduction and identify a low-affinity K+ release site in KdpB, refining how ions traverse from KdpA to KdpB and are released to the cytoplasm. URL: https://doi.org/10.1101/2025.05.05.652293 (May 2025). (hussein2025conductionpathwayfor pages 1-4)
- Updated mechanism and regulation from recent reviews: The intersubunit transport model, residue-level roles (e.g., F232, D583, K586 in KdpB), and lipid dependence (cardiolipin at KdpA–KdpB interface) are emphasized, alongside a regulatory brake via phosphorylation of KdpB S162 that traps the complex in an E1P off-cycle state at high K+. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
- Discovery of tandem serine–histidine kinase activity in KdpD: KdpD both transcriptionally activates kdpFABC via its histidine kinase function under low K+ and post-translationally inhibits the pump at high K+ by directly phosphorylating KdpB at S162 via an N-terminal atypical serine kinase (ASK) domain. URL: https://doi.org/10.1038/s41467-024-47526-8 (April 2024); preprint version: https://doi.org/10.1101/2023.11.09.566405 (Nov 2023). (silberberg2024kdpdisa pages 2-4, silberberg2023sensorykinasekdpd pages 16-19)
3) Function, localization, and pathway context (with focus on KdpC)
- Function within the transporter: KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface, indirectly tuning K+ entry into the intersubunit tunnel. This aligns with its conserved family/domain assignment (PF02669/IPR003820) and periplasmic topology. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
- Subcellular localization: Periplasmically oriented, single-pass membrane protein embedded with KdpA/KdpB/KdpF in the cytoplasmic membrane. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
- Pathway context: KdpFABC mediates high-affinity K+ uptake under limitation, controlled by the KdpDE two-component system. KdpD integrates signals (including K+ and, in some species, c-di-AMP) to regulate kdpFABC both transcriptionally and post-translationally by KdpB S162 phosphorylation. URLs: https://doi.org/10.1038/s41467-024-47526-8 (Apr 2024); https://doi.org/10.1101/2023.11.09.566405 (Nov 2023). (silberberg2024kdpdisa pages 2-4, silberberg2023sensorykinasekdpd pages 16-19)
4) Regulation under high vs. low K+
- Low K+: KdpD’s histidine kinase activates KdpE, driving kdpFABC expression and thereby increasing high-affinity K+ uptake via KdpFABC. Review context supports induction under K+ limitation/osmotic stress. URLs: https://doi.org/10.1042/bst20221543 (June 2023); https://doi.org/10.1038/s41467-024-47526-8 (Apr 2024). (stock2023fastforwardonptype pages 4-6, silberberg2024kdpdisa pages 2-4)
- High K+: KdpD’s N-terminal ASK domain phosphorylates KdpB at S162 to inhibit ATPase turnover by preventing the E1P→E2P transition (electrostatic conflict with D307-P), thus avoiding wasteful ATP consumption. Species diversity exists: in some bacteria, c-di-AMP modulates this ASK activity. URLs: https://doi.org/10.1038/s41467-024-47526-8 (Apr 2024); https://doi.org/10.1101/2023.11.09.566405 (Nov 2023). (silberberg2024kdpdisa pages 2-4, silberberg2023sensorykinasekdpd pages 16-19)
5) Quantitative/statistical details
- Cryo-EM resolution/state: 2.1 Å E1~P·ADP state in nanodiscs; K+ densities at KdpA SF and KdpB CBS; D307 phosphorylation and ADP + two Mg2+ in N-domain observed. URL: https://doi.org/10.1101/2025.05.05.652293 (May 2025). (hussein2025conductionpathwayfor pages 1-4)
- Conduction pathway length and residues: ~40 Å intersubunit tunnel; key KdpB residues F232, D583, K586; catalytic aspartate D307 cycles through phosphorylation. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
- Regulatory phosphorylation site: KdpB S162 directly phosphorylated by KdpD’s ASK; mutation of Walker A in the ASK domain abolishes S162 phosphorylation and relieves inhibition. URL: https://doi.org/10.1038/s41467-024-47526-8 (Apr 2024). (silberberg2024kdpdisa pages 2-4)
6) Applicability to Desulfovibrio vulgaris Hildenborough (DVU_3337; Q725T8)
- Conservation and inference: KdpC is a conserved periplasmic single-spanning subunit (PF02669/IPR003820). Given the conservation of the KdpFABC architecture and KdpC family membership, DVU_3337 (kdpC) is expected to localize to the cytoplasmic membrane with a periplasmic orientation and to function structurally/modulatorily in high-affinity K+ uptake under K+ limitation. Direct organism-specific structural/biochemical data were not retrieved in the present corpus; conclusions are inferred from cross-species conservation and contemporary mechanistic models. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
- Regulatory framework: Many bacteria use KdpDE; the newly described KdpD ASK-mediated post-translational inhibition is widespread, with species-specific inputs (e.g., c-di-AMP). Desulfovibrio spp. may share this regulatory architecture, but explicit demonstration in D. vulgaris Hildenborough was not identified here; this remains an inference pending species-specific confirmation. URLs: https://doi.org/10.1038/s41467-024-47526-8 (Apr 2024); https://doi.org/10.1101/2023.11.09.566405 (Nov 2023). (silberberg2024kdpdisa pages 2-4, silberberg2023sensorykinasekdpd pages 16-19)
7) Current applications and implementations
- Structural and mechanistic benchmarking: KdpFABC serves as a model for intersubunit ion transfer coupled to a P-type ATPase cycle, widely used in cryo-EM method development and mechanistic dissection of ion pumps, including lipid cofactor requirements (e.g., cardiolipin). This informs general strategies for studying membrane protein lipid interactions and transporter regulation. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
8) Expert perspectives
- Reviews emphasize the uniqueness of KdpFABC among P-type ATPases: the intersubunit tunnel linking a channel-like selectivity filter (KdpA) to a P-type ATPase motor (KdpB) and nuanced multilayer regulation (transcriptional via KdpDE and post-translational via KdpD ASK on KdpB S162). This combination is cited as a paradigmatic example of mixed-domain transport and regulation. URL: https://doi.org/10.1042/bst20221543 (June 2023). (stock2023fastforwardonptype pages 4-6)
Embedded evidence summary table
| Topic | Key finding | Quantitative details | Species/system | Method | Source (URL; date) |
|---|---|---:|---|---|---|
| Intersubunit tunnel & conduction path | K+ transits an intersubunit tunnel from KdpA selectivity filter to KdpB canonical binding site; tunnel central to pump mechanism | ~40 Å tunnel; ~18 cryo-EM structures referenced; residues implicated: F232, D583, K586 | E. coli KdpFABC (model for bacterial systems) | Cryo-EM, MD simulations, mutagenesis, transport/ATPase assays | https://doi.org/10.1042/bst20221543; Jun 2023; and https://doi.org/10.1101/2025.05.05.652293; May 2025 (stock2023fastforwardonptype pages 4-6, hussein2025conductionpathwayfor pages 1-4) |
| E1~P·ADP 2.1 Å cryo-EM state with K+ at KdpA SF and KdpB CBS | High-resolution map shows K+ densities in KdpA selectivity filter and at KdpB canonical binding site; catalytic Asp307 phosphorylated (E1~P·ADP) | 2.1 Å resolution; D307-P observed; ADP + Mg2+ in N-domain; supports Post-Albers-like cycle | E. coli KdpFABC (nanodisc reconstitution) | Cryo-EM under turnover conditions; ATPase and ion transport assays | https://doi.org/10.1101/2025.05.05.652293; May 2025 (hussein2025conductionpathwayfor pages 1-4) |
| Mechanistic model & role of KdpC (periplasmic single-pass) | KdpC is a periplasmically oriented single-pass subunit that modulates ion access and stabilizes assembly; exact catalytic role unclear (likely structural/chaperone) | Annotated as KdpC family (PF02669 / IPR003820); periplasmic single-spanner | E. coli and broadly conserved bacterial KdpFABC | Literature review and structural analyses | https://doi.org/10.1042/bst20221543; Jun 2023 (stock2023fastforwardonptype pages 4-6) |
| Post-translational inhibition: KdpB S162 phosphorylation by KdpD ASK | KdpD's atypical serine kinase domain phosphorylates KdpB at S162, inhibiting E1P→E2P transition and preventing wasteful ATP hydrolysis | Phospho-site: KdpB S162; inhibitory mechanism: electrostatic conflict between D307-P and S162-P demonstrated by mutagenesis/assays | Demonstrated in bacterial systems (E. coli evidence) | Biochemical assays, phosphoprotein analysis, mutagenesis, in vivo/in vitro experiments | https://doi.org/10.1038/s41467-024-47526-8; Apr 2024 (silberberg2024kdpdisa pages 2-4) |
| Dual transcriptional/post-translational control by KdpD; c-di-AMP regulation | KdpD is a tandem ASK–HK sensor that both regulates kdpFABC transcriptionally (via HK) and post-translationally (via ASK); c-di-AMP can modulate ASK activity in some species | KdpD architecture: N-terminal ASK + Usp domain; C-terminal DHp/CA transmitter; Walker A motif in ASK required for KdpB S162 phosphorylation | Multiple bacteria (mechanistic diversity across species) | Genetics, biochemical reconstitution, signaling assays | https://doi.org/10.1038/s41467-024-47526-8; Apr 2024; and https://doi.org/10.1101/2023.11.09.566405; Nov 2023 (silberberg2024kdpdisa pages 2-4, silberberg2023sensorykinasekdpd pages 16-19) |
| P-type ATPase context & lipid dependence (cardiolipin) | KdpB is a P-type ATPase subunit operating via a Post-Albers-like cycle; intersubunit transport model is a notable exception; cardiolipin at the KdpA–KdpB interface is essential for activity | Cardiolipin required for activity; transport cycle follows P-type ATPase scheme; intersubunit tunnel unique feature | E. coli KdpFABC; general P-type ATPase overview | Review of recent structural/functional studies (cryo-EM focused) | https://doi.org/10.1042/bst20221543; Jun 2023 (stock2023fastforwardonptype pages 4-6) |
Table: Compact table linking 2023–2025 structural and regulatory findings about the KdpFABC pump and KdpC, with quantitative details, methods, species, and primary sources; useful for tracing evidence on KdpC's putative structural role and KdpFABC regulation (citations provided).
Limitations and open questions
- KdpC’s precise mechanistic contribution beyond structural/assembly and periplasmic gating remains incompletely defined at atomic detail relative to KdpA/KdpB; continued targeted mutagenesis and subunit-specific cryo-EM analyses are warranted. (stock2023fastforwardonptype pages 4-6)
- Species-specific validation in D. vulgaris Hildenborough (DVU_3337) is needed to confirm regulatory inputs (e.g., c-di-AMP effects on KdpD) and any unique lipid dependencies.
Conclusion
kdpC (DVU_3337; UniProt Q725T8) encodes the periplasmic, single-pass KdpC subunit of the KdpFABC high-affinity K+ pump. Contemporary work establishes a conduction pathway from KdpA to KdpB and reveals a dual regulatory regime wherein KdpD activates kdpFABC expression at low K+ and directly inhibits pump turnover at high K+ by phosphorylating KdpB S162 via an atypical serine kinase domain. While KdpC’s role is primarily structural/modulatory, its conservation supports analogous function in D. vulgaris Hildenborough. URLs: Stock 2023 https://doi.org/10.1042/bst20221543; Silberberg 2024 https://doi.org/10.1038/s41467-024-47526-8; Silberberg 2023 preprint https://doi.org/10.1101/2023.11.09.566405; Hussein 2025 preprint https://doi.org/10.1101/2025.05.05.652293. (stock2023fastforwardonptype pages 4-6, silberberg2024kdpdisa pages 2-4, silberberg2023sensorykinasekdpd pages 16-19, hussein2025conductionpathwayfor pages 1-4)
References
(stock2023fastforwardonptype pages 4-6): Charlott Stock, Tomáš Heger, Sara Basse Hansen, Sigrid Thirup Larsen, Michael Habeck, Thibaud Dieudonné, Ronja Driller, and Poul Nissen. Fast-forward on p-type atpases: recent advances on structure and function. Biochemical Society transactions, 51:1347-1360, Jun 2023. URL: https://doi.org/10.1042/bst20221543, doi:10.1042/bst20221543. This article has 25 citations and is from a peer-reviewed journal.
(hussein2025conductionpathwayfor pages 1-4): Adel Hussein, Xihui Zhang, Bjørn Panyella Pedersen, and David L. Stokes. Conduction pathway for potassium through the e. coli pump kdpfabc. bioRxiv, May 2025. URL: https://doi.org/10.1101/2025.05.05.652293, doi:10.1101/2025.05.05.652293. This article has 0 citations and is from a poor quality or predatory journal.
(silberberg2024kdpdisa pages 2-4): Jakob M. Silberberg, Sophie Ketter, Paul J. N. Böhm, Kristin Jordan, Marcel Wittenberg, Julia Grass, and Inga Hänelt. Kdpd is a tandem serine histidine kinase that controls k+ pump kdpfabc transcriptionally and post-translationally. Nature Communications, Apr 2024. URL: https://doi.org/10.1038/s41467-024-47526-8, doi:10.1038/s41467-024-47526-8. This article has 7 citations and is from a highest quality peer-reviewed journal.
(silberberg2023sensorykinasekdpd pages 16-19): Jakob M Silberberg, Sophie Ketter, Paul JN Böhm, Kristin Jordan, Marcel Wittenberg, Julia Grass, and Inga Hänelt. Sensory kinase kdpd is a tandem serine histidine kinase controlling k+ pump kdpfabc on the translational and post-transcriptional level. bioRxiv, Nov 2023. URL: https://doi.org/10.1101/2023.11.09.566405, doi:10.1101/2023.11.09.566405. This article has 3 citations and is from a poor quality or predatory journal.
id: Q725T8
gene_symbol: kdpC
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:882
label: Nitratidesulfovibrio vulgaris Hildenborough
description: >
KdpC is a periplasmic, single-pass membrane subunit of the KdpFABC high-affinity
potassium-transporting ATPase complex. It functions as a catalytic chaperone that
increases the ATP-binding affinity of the ATPase subunit KdpB by forming a transient
KdpB/KdpC/ATP ternary complex. KdpC does not itself possess catalytic ATPase or
hydrolase activity; rather, it modulates ion access in the periplasmic vestibule
and stabilizes complex assembly. The KdpFABC complex is induced under potassium
limitation to enable high-affinity K+ uptake (Stock et al., 2023).
existing_annotations:
- term:
id: GO:0071805
label: potassium ion transmembrane transport
evidence_type: IEA
original_reference_id: GO_REF:0000118
review:
summary: >
KdpC is part of the KdpFABC complex which transports potassium ions across the
membrane. While KdpC does not directly catalyze ion transport (this is performed
by KdpA/KdpB), it is an essential accessory subunit required for complex function.
The annotation correctly reflects KdpC's involvement in the biological process.
action: ACCEPT
reason: >
KdpC is an essential subunit of the KdpFABC potassium-transporting ATPase.
Contemporary structural and mechanistic studies confirm that KdpC is required
for proper complex function, even though it does not directly catalyze transport.
The 'involved_in' qualifier is appropriate for an accessory subunit that enables
the process through its catalytic chaperone function.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "KdpC subunit role/definition: KdpC is periplasmically oriented and single-pass. Contemporary models assign KdpC a non-catalytic but essential structural/modulatory role"
- term:
id: GO:0000166
label: nucleotide binding
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: >
This annotation is based on UniProtKB keyword mapping (KW-0547). The annotation
is misleading for KdpC. While KdpC participates in forming a transient ternary
complex with KdpB and ATP, it is KdpB that directly binds ATP. KdpC functions
as a catalytic chaperone to increase ATP-binding affinity of KdpB, but does
not itself possess intrinsic nucleotide-binding capability.
action: REMOVE
reason: >
KdpC does not directly bind nucleotides. The UniProt HAMAP annotation states
that KdpC "increases the ATP-binding affinity of the ATP-hydrolyzing subunit
KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex." This
describes an indirect role in modulating ATP binding to KdpB, not direct
nucleotide binding by KdpC itself. The cryo-EM structures show ADP and Mg2+
bound in the KdpB N-domain, not KdpC. This is an over-annotation resulting
from keyword propagation that does not accurately reflect KdpC's molecular function.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex"
- term:
id: GO:0005524
label: ATP binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >
This annotation derives from UniRule:UR000058586 and keyword mapping. Like
the nucleotide binding annotation, this is an over-annotation. KdpC participates
in ternary complex formation with KdpB and ATP, but does not itself directly
bind ATP. The ATP-binding site resides in KdpB, not KdpC.
action: REMOVE
reason: >
KdpC is not an ATP-binding protein. The catalytic aspartate (D307) that becomes
phosphorylated during the reaction cycle is located in KdpB, and ATP/ADP are
bound to the KdpB N-domain. KdpC's role is to enhance ATP-binding affinity
of KdpB through allosteric/chaperone mechanisms, not to directly bind ATP.
This annotation incorrectly attributes to KdpC a molecular function that
belongs to KdpB.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "KdpB is the P-type ATPase motor"
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "D307 phosphorylated and ADP + two Mg2+ bound in the N-domain"
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >
KdpC is localized to the bacterial inner membrane (equivalent to plasma membrane)
as a single-pass membrane protein with periplasmic orientation. This annotation
is correct and well-supported.
action: ACCEPT
reason: >
Multiple sources confirm KdpC is a membrane protein. UniProt HAMAP annotation
states "Cell inner membrane; Single-pass membrane protein." Structural studies
confirm KdpC is periplasmically oriented and embedded in the cytoplasmic membrane.
For bacteria, the inner/cytoplasmic membrane corresponds to GO:0005886 plasma membrane.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "Cell inner membrane"
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "Periplasmically oriented, single-pass membrane protein embedded with KdpA/KdpB/KdpF in the cytoplasmic membrane"
- term:
id: GO:0006811
label: monoatomic ion transport
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: >
This annotation is too general. KdpC is specifically involved in potassium ion
transport as part of the KdpFABC complex. The more specific term GO:0006813
(potassium ion transport) is already annotated.
action: MARK_AS_OVER_ANNOTATED
reason: >
While technically correct (potassium is a monoatomic ion), this annotation
adds no information beyond what GO:0006813 (potassium ion transport) and
GO:0071805 (potassium ion transmembrane transport) already provide. The
KdpFABC complex is specifically a potassium transporter, not a general ion
transporter. Retaining this broader term alongside the specific terms is
redundant. However, this is not incorrect per se - just uninformative.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump induced under K+ limitation/osmotic stress"
- term:
id: GO:0006813
label: potassium ion transport
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >
KdpC is an essential subunit of the KdpFABC high-affinity potassium transport
system. This biological process annotation is appropriate.
action: ACCEPT
reason: >
KdpC is required for proper function of the KdpFABC complex, which mediates
high-affinity K+ uptake. The annotation correctly captures KdpC's involvement
in the biological process of potassium ion transport. However, GO:0071805
(potassium ion transmembrane transport) is more specific and also present,
so this annotation is somewhat redundant but not incorrect.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "Part of the high-affinity ATP-driven potassium transport (or Kdp) system"
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "KdpFABC mediates high-affinity K+ uptake under limitation"
- term:
id: GO:0008556
label: P-type potassium transmembrane transporter activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >
This molecular function annotation is inappropriate for KdpC. GO:0008556
describes the enzymatic transporter activity, which in the KdpFABC complex
is performed by KdpB (the P-type ATPase) together with KdpA (the K+ channel).
KdpC does not possess transporter activity; it is an accessory subunit with
a regulatory/chaperone role.
action: MODIFY
reason: >
GO:0008556 is defined as "Enables the transfer of a solute... according to
the reaction: ATP + H2O + K+(out) = ADP + phosphate + K+(in)." This describes
catalytic activity that KdpC does not possess. KdpB is the ATPase that
hydrolyzes ATP (containing the catalytic aspartate D307), and KdpA is the
K+ translocase. KdpC functions as a "catalytic chaperone" that modulates
KdpB activity but does not itself catalyze transport. This annotation
incorrectly attributes complex activity to an individual subunit that
lacks the catalytic machinery.
proposed_replacement_terms:
- id: GO:0001671
label: ATPase activator activity
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB"
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface"
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >
This general membrane annotation is correct but redundant given the more
specific GO:0005886 (plasma membrane) annotation already present.
action: KEEP_AS_NON_CORE
reason: >
KdpC is indeed a membrane protein, so this annotation is not incorrect.
However, GO:0005886 (plasma membrane) is more specific and accurately
describes KdpC's localization. This broader term adds no additional
information. It derives from InterPro domain IPR003820 which appropriately
associates KdpC with membranes.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "Single-pass membrane protein"
- term:
id: GO:0016787
label: hydrolase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: >
This annotation is incorrect for KdpC. The hydrolase (ATPase) activity in
the KdpFABC complex resides in KdpB, not KdpC. KdpC does not possess
catalytic hydrolase activity.
action: REMOVE
reason: >
The ATPase activity (ATP hydrolysis) is carried out by KdpB, which contains
the catalytic aspartate D307 that becomes phosphorylated during the P-type
ATPase cycle. KdpC has no catalytic residues and functions as a regulatory/
chaperone subunit. The UniProtKB keyword "Hydrolase" (KW-0378) was incorrectly
propagated to KdpC, likely because the KdpFABC complex has hydrolase activity.
This conflates complex function with individual subunit function. KdpC
"acts as a catalytic chaperone" but is not itself a catalyst.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "catalytic aspartate D307 cycles through phosphorylation"
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB"
# Proposed new annotations based on KdpC's actual function
- term:
id: GO:0031004
label: potassium ion-transporting ATPase complex
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: >
KdpC is part of the KdpFABC potassium ion-transporting ATPase complex.
GO:0031004 specifically describes this complex in E. coli, noting that
"KdpC and KdpF seem to be involved in assembly and stabilization of the
complex."
action: NEW
reason: >
This cellular component term precisely describes KdpC's localization as
part of a defined protein complex. The GO term definition explicitly
mentions KdpC: "The E. coli complex consists of 4 proteins: KdpA is the
potassium ion translocase, KdpB is the ATPase, and KdpC and KdpF seem to
be involved in assembly and stabilization of the complex." This is more
informative than the generic membrane terms currently annotated.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "The system is composed of three essential subunits: KdpA, KdpB and KdpC"
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump"
- term:
id: GO:0001671
label: ATPase activator activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: >
KdpC functions as a catalytic chaperone that increases ATP-binding affinity
and promotes ATPase activity of KdpB. GO:0001671 ("Binds to and increases
the activity of an ATP hydrolysis activity") accurately describes this
molecular function.
action: NEW
reason: >
This molecular function term accurately captures KdpC's primary role in
the KdpFABC complex. Unlike the incorrect annotations of ATP binding or
hydrolase activity, this term describes KdpC's actual regulatory function
of enhancing KdpB's ATPase activity through formation of a transient
ternary complex. This is supported by UniProt HAMAP annotation and
contemporary structural studies.
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex"
- reference_id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
supporting_text: "KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface"
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings:
- statement: InterPro domain IPR003820 (KdpC) correctly associates with membrane localization
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings:
- statement: Keyword propagation resulted in over-annotation of nucleotide binding and hydrolase activity to KdpC
- statement: These keywords apply to the KdpFABC complex or specifically to KdpB, not to KdpC
- id: GO_REF:0000118
title: TreeGrafter-generated GO annotations
findings:
- statement: Biological process annotation for potassium ion transmembrane transport is appropriate
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings:
- statement: Some annotations conflate complex-level function with individual subunit function
- statement: ATP binding, P-type transporter activity, and hydrolase activity belong to KdpB, not KdpC
- id: GO_REF:0000024
title: Method traceable to sequence similarity
findings:
- statement: Used for new annotations based on HAMAP family membership and literature
- id: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md
title: Deep research report on KdpC function in D. vulgaris Hildenborough
findings:
- statement: KdpC is a catalytic chaperone that increases ATP-binding affinity of KdpB
supporting_text: "KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface"
- statement: KdpC forms transient KdpB/KdpC/ATP ternary complex
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex"
- statement: KdpC is periplasmically oriented and single-pass
supporting_text: "Periplasmically oriented, single-pass membrane protein embedded with KdpA/KdpB/KdpF in the cytoplasmic membrane"
- statement: KdpC role is non-catalytic but essential for complex function
supporting_text: "Contemporary models assign KdpC a non-catalytic but essential structural/modulatory role"
- id: file:DESVH/Q725T8/Q725T8-uniprot.txt
title: UniProt entry for Q725T8 (KdpC)
findings:
- statement: KdpC acts as a catalytic chaperone for KdpB
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex"
- statement: KdpC is a single-pass membrane protein in the cell inner membrane
supporting_text: "Cell inner membrane"
- statement: KdpC is part of the KdpFABC complex
supporting_text: "The system is composed of three essential subunits: KdpA, KdpB and KdpC"
- id: PMID:37264943
title: "Fast-forward on P-type ATPases: recent advances on structure and function"
findings:
- statement: Review of KdpFABC intersubunit transport model
supporting_text: "we outline the new intersubunit transport model of KdpFABC"
- id: PMID:38622146
title: "KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC"
findings:
- statement: Regulatory control of KdpFABC by KdpD
supporting_text: "KdpD additionally mediates an inhibitory serine phosphorylation of KdpFABC at high potassium levels"
core_functions:
- description: >
KdpC acts as a catalytic chaperone that increases the ATP-binding affinity
of KdpB by forming a transient KdpB/KdpC/ATP ternary complex, thereby
promoting ATP hydrolysis and K+ transport.
molecular_function:
id: GO:0001671
label: ATPase activator activity
directly_involved_in:
- id: GO:0071805
label: potassium ion transmembrane transport
locations:
- id: GO:0005886
label: plasma membrane
in_complex:
id: GO:0031004
label: potassium ion-transporting ATPase complex
supported_by:
- reference_id: file:DESVH/Q725T8/Q725T8-uniprot.txt
supporting_text: "This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex"
proposed_new_terms: []
suggested_questions:
- question: Does KdpC directly contact ATP in the ternary complex, or does it act purely through allosteric effects on KdpB?
- question: Is there structural data specific to D. vulgaris KdpFABC that would confirm conservation of KdpC's role?
suggested_experiments:
- description: >
Cryo-EM structure of KdpFABC with focus on KdpC-ATP proximity to determine
if KdpC directly contacts ATP in the ternary complex.
hypothesis: KdpC may directly contact ATP to facilitate its binding to KdpB
- description: >
KdpC mutagenesis affecting KdpB ATPase activity to identify KdpC residues
critical for its catalytic chaperone function.
hypothesis: Specific KdpC residues at the KdpB interface are required for ATPase activation