DVU_1606 (Q72BM9) is a TrkA-family potassium uptake regulatory protein containing RCK_N and RCK_C domains. Based on structural homology to characterized KtrA/TrkA proteins from other bacteria, it functions as the cytosolic regulatory subunit of a Trk/Ktr K+ uptake system. The protein assembles into an octameric RCK gating ring that associates with a membrane-embedded TrkH/KtrB pore. ATP binding promotes an active square-like conformation that opens the pore for K+ flux, while ADP binding induces an inactive diamond-like conformation. Na+ binding at intra-dimer sites synergistically stabilizes the active state. The protein may also bind c-di-AMP, which typically reduces K+ import by destabilizing regulator-pore interactions. The core physiological role is regulation of K+ homeostasis and osmoadaptation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0098655
monoatomic cation transmembrane transport
|
IEA
GO_REF:0000108 |
MODIFY |
Summary: This annotation was inferred from GO:0008324 (transporter activity) via logical inference. However, Q72BM9 is NOT the membrane transporter itself but the cytosolic regulatory RCK subunit that gates the TrkH/KtrB pore. While the protein is involved in regulating cation transport, it does not itself participate in the transmembrane transport process. The annotation should be modified to reflect regulatory involvement rather than direct transport.
Reason: TrkA/KtrA family proteins are cytosolic regulatory subunits that form octameric RCK gating rings to modulate the activity of membrane K+ pores (TrkH/KtrB). Cryo-EM structures of B. subtilis KtrAB at 2.8 A resolution demonstrate that KtrA forms an octameric ring bound to dimeric KtrB, with ATP/ADP binding controlling pore gating rather than direct transport (Chiang et al. 2024). The protein regulates K+ transmembrane transport but does not itself transport ions across the membrane.
Proposed replacements:
regulation of potassium ion transmembrane transport
Supporting Evidence:
file:DESVH/Q72BM9/Q72BM9-deep-research-falcon.md
DVU_1606 (TrkA-family RCK protein) is a cytosolic/peripheral protein that assembles into an octameric RCK gating ring associated with an inner-membrane K+ pore
DOI:10.1038/s41467-024-48057-y
2024 cryo-EM structures of Bacillus subtilis KtrAB (2.8 A) show an octameric KtrA RCK ring bound to a dimeric KtrB pore. ATP-bound KtrA adopts a square-like active conformation; ADP-bound adopts a diamond-like inactive state.
DOI:10.1128/mmbr.00181-23
The cytosolic component (TrkA/KtrA/KtrC) is a ring-like assembly of RCK (Regulator of Conductance of K+) domains that gates the pore in response to ligands.
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000044 |
MODIFY |
Summary: This annotation derives from UniProtKB subcellular location vocabulary mapping, which incorrectly predicts Q72BM9 as a multi-pass membrane protein based on Phobius transmembrane helix predictions. However, characterized TrkA/KtrA homologs are cytosolic proteins that associate with the membrane pore peripherally via protein-protein interactions, not as integral membrane proteins. The RCK domains (positions 127-350) are clearly cytosolic based on structural data from homologs.
Reason: Structural biology of KtrA/TrkA proteins demonstrates they are cytosolic regulatory subunits. The 2024 cryo-EM structure of B. subtilis KtrAB shows KtrA as a cytosolic octameric ring that binds to the cytoplasmic face of the KtrB membrane pore. The RCK_N and RCK_C domains that comprise the functional core of this protein are well-established as cytosolic ligand-binding domains. While Phobius predicts two N-terminal transmembrane helices, the dominant functional domains are cytosolic, and the protein should be annotated to cytoplasm with peripheral association to the plasma membrane.
Proposed replacements:
cytoplasm
Supporting Evidence:
DOI:10.1038/s41467-024-48057-y
By homology to experimentally resolved complexes, DVU_1606 (TrkA-family RCK protein) is a cytosolic/peripheral protein that assembles into an octameric RCK gating ring associated with an inner-membrane K+ pore (TrkH/KtrB homolog) via cytosolic interfaces. The active transport relies on membrane potential; the RCK ring does not span the membrane.
|
|
GO:0006813
potassium ion transport
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: This annotation from InterPro (IPR003148, IPR006037, IPR036721) captures the involvement of Q72BM9 in potassium ion transport. While the protein does not directly transport K+, it is an essential regulatory component of the K+ uptake system. The term GO:0006813 is appropriately general (covering both direct transport and regulatory involvement) and is acceptable, though a more specific regulatory term would be more informative.
Reason: GO:0006813 (potassium ion transport) describes the directed movement of K+ ions by means of transporters or pores, which includes regulatory subunits that are essential for this process. TrkA/KtrA proteins are obligate components of the functional Trk/Ktr K+ uptake system, and without them the pore cannot be properly gated. The annotation is acceptable as it captures the biological process in which the protein participates, even though its specific role is regulatory rather than catalytic.
Supporting Evidence:
DOI:10.1128/mmbr.00181-23
Trk/Ktr potassium uptake systems: Two-component assemblies mediating low- to moderate-affinity K+ uptake that is primarily energized by the membrane potential. The membrane component (TrkH/KtrB/KtrD) forms the K+ permeation pathway, and the cytosolic component (TrkA/KtrA/KtrC) is a ring-like assembly of RCK domains that gates the pore in response to ligands.
|
|
GO:0008324
monoatomic cation transmembrane transporter activity
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: This MF annotation from InterPro (IPR006037 - RCK_C) is an over-annotation. Q72BM9 is the regulatory RCK subunit, NOT the membrane transporter itself. RCK domains bind nucleotides (ATP/ADP) and undergo conformational changes that regulate the associated membrane pore, but they do not themselves enable transmembrane transport. The appropriate MF annotation would be potassium channel regulator activity or transporter regulator activity.
Reason: Transporter activity terms should be reserved for proteins that directly enable the movement of substrates across membranes. TrkA/KtrA RCK proteins regulate transporter activity by binding to and modulating the TrkH/KtrB membrane pore. The 2024 structural study demonstrates that KtrA binds ATP/ADP at RCK interfaces and undergoes square-to-diamond conformational transitions that mechanically gate the associated pore. This is regulator activity, not transporter activity. The most appropriate term is GO:0015459 (potassium channel regulator activity) which specifically describes proteins that bind to and modulate K+ channels/transporters.
Proposed replacements:
potassium channel regulator activity
ATP binding
Supporting Evidence:
DOI:10.1038/s41467-024-48057-y
ATP binding to RCK_N intra-dimer interfaces stabilizes an activating square ring conformation; ADP stabilizes an inactivating diamond conformation, switching K+ flux on/off through mechanical coupling to the pore's intramembrane gate.
DOI:10.1099/mic.0.001597
In Streptococcus mitis, TrkA directly binds c-di-AMP and is required for growth under low K+. Loss of TrkA compromises growth and modulates cellular c-di-AMP levels, reinforcing TrkA's role in c-di-AMP-mediated K+ control.
|
|
GO:0015459
potassium channel regulator activity
|
ISS
DOI:10.1038/s41467-024-48057-y |
NEW |
Summary: NEW annotation. Based on structural and functional characterization of homologous KtrA proteins, Q72BM9 functions as a potassium channel/transporter regulator. It binds to and modulates the activity of the associated TrkH/KtrB K+ pore through nucleotide-dependent conformational changes.
Reason: The core molecular function of TrkA/KtrA proteins is to regulate the activity of associated K+ transporters. GO:0015459 (potassium channel regulator activity) accurately captures this function. Evidence from structural studies of B. subtilis KtrAB demonstrates that KtrA binds to KtrB and modulates its activity through ATP/ADP-dependent conformational changes.
Supporting Evidence:
DOI:10.1038/s41467-024-48057-y
A functional Ktr/Trk complex comprises a TrkH/KtrB-type dimeric membrane pore and a TrkA/KtrA-type octameric regulator. ATP-bound KtrA adopts a square-like active conformation; ADP-bound adopts a diamond-like inactive state.
|
|
GO:0005524
ATP binding
|
ISS
DOI:10.1038/s41467-024-48057-y |
NEW |
Summary: NEW annotation. The RCK_N domain of TrkA/KtrA proteins contains ATP/ADP binding sites that are essential for the regulatory function. ATP binding at intra-dimer interfaces stabilizes the active conformation.
Reason: ATP binding is a core biochemical function of TrkA/KtrA RCK proteins. The NAD(P)-binding domain superfamily signature (IPR036291) and structural studies confirm nucleotide binding capability. ATP/ADP binding is the primary mechanism by which these proteins sense cellular energy status and regulate K+ uptake accordingly.
Supporting Evidence:
DOI:10.1038/s41467-024-48057-y
ATP binding to RCK_N intra-dimer interfaces stabilizes an activating square ring conformation; ADP stabilizes an inactivating diamond conformation.
|
|
GO:0180001
cyclic-di-AMP binding
|
ISS
DOI:10.1128/mmbr.00181-23 |
NEW |
Summary: NEW annotation. TrkA/KtrA proteins are known receptors for c-di-AMP, a bacterial second messenger that regulates K+ homeostasis. c-di-AMP binding to RCK domains typically reduces K+ import by destabilizing regulator-pore interactions.
Reason: c-di-AMP is a master regulator of K+ homeostasis in bacteria, and TrkA/KtrA RCK proteins are established c-di-AMP receptors. Direct binding has been demonstrated for TrkA in S. mitis (Vevik 2025). The binding affinities range from ~40 nM to low uM across different systems. This is a likely function for Q72BM9 based on conservation of the RCK domain architecture.
Supporting Evidence:
DOI:10.1128/mmbr.00181-23
c-di-AMP binds many RCK/CBS-containing K+ transport regulators (including TrkA/KtrA/KtrC), with affinities spanning ~40 nM to low uM, and reduces K+ import by destabilizing regulator-pore interactions.
DOI:10.1099/mic.0.001597
In Streptococcus mitis, TrkA directly binds c-di-AMP and is required for growth under low K+.
|
Q: What is the cognate TrkH/KtrB membrane pore partner for DVU_1606 in D. vulgaris?
Q: Does DVU_1606 bind c-di-AMP, and if so, with what affinity?
Q: Is there evidence for Na+ synergy in DVU_1606 function as seen in B. subtilis KtrA?
Experiment: Isothermal titration calorimetry to measure ATP, ADP, and c-di-AMP binding affinities
Hypothesis: DVU_1606 binds ATP with higher affinity than ADP, and also binds c-di-AMP
Experiment: Co-immunoprecipitation or bacterial two-hybrid to identify the cognate membrane pore partner
Hypothesis: DVU_1606 interacts with a TrkH/KtrB homolog in D. vulgaris
Experiment: Cryo-EM structure of DVU_1606 octameric ring to confirm conservation of gating mechanism
Hypothesis: DVU_1606 forms an octameric ring similar to B. subtilis KtrA
Experiment: K+ uptake assays in D. vulgaris DVU_1606 deletion mutant under various osmotic conditions
Hypothesis: DVU_1606 is required for efficient K+ uptake and osmoadaptation
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model: Edison Scientific Literature
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start_time: '2026-01-15T10:40:04.404997'
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template_variables:
organism: DESVH
gene_id: Q72BM9
gene_symbol: Q72BM9
uniprot_accession: Q72BM9
protein_description: 'SubName: Full=Potassium uptake protein, TrkA family {ECO:0000313|EMBL:AAS96084.1};'
gene_info: OrderedLocusNames=DVU_1606 {ECO:0000313|EMBL:AAS96084.1};
organism_full: Nitratidesulfovibrio vulgaris (strain ATCC 29579 / DSM 644 / CCUG
34227 / NCIMB 8303 / VKM B-1760 / Hildenborough) (Desulfovibrio vulgaris).
protein_family: Not specified in UniProt
protein_domains: K_chnl_dom. (IPR013099); NAD(P)-bd_dom_sf. (IPR036291); RCK_C.
(IPR006037); RCK_C_sf. (IPR036721); RCK_N. (IPR003148)
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citation_count: 15
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 'Q72BM9' 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 Q72BM9 (gene ID: Q72BM9, UniProt: Q72BM9) 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 'Q72BM9' 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 Q72BM9 (gene ID: Q72BM9, UniProt: Q72BM9) 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.
Research plan (summary)
- Verify target identity and domains from the provided UniProt context and align with literature on Trk/Ktr systems.
- Synthesize current mechanistic understanding of Trk/Ktr (architecture, gating, ligands), emphasizing 2023–2024 sources.
- Map likely cellular localization and complex composition for DVU_1606 by homology.
- Summarize physiological roles, regulation by c-di-AMP, and quantitative parameters from recent studies.
- Note DVU-specific evidence and limitations.
Gene/protein verification and scope
- Identity: The target is DVU_1606 (UniProt Q72BM9) from Desulfovibrio vulgaris Hildenborough, annotated as a TrkA-family potassium uptake protein with RCK (KTN) domains. This aligns with the canonical TrkA/KtrA cytosolic regulatory subunits that assemble with TrkH/KtrB membrane pores to mediate K+ uptake in bacteria (architecture detailed below). No conflicting gene symbol usage was found in the retrieved literature; we proceed under the DVU_1606 annotation provided. Inference-based conclusions are made where DVU-specific data are lacking (see Limitations). (foster2024bacterialcellvolume pages 6-8, chiang2024structuralbasisand pages 1-2)
1) Key concepts and definitions (current understanding)
- Trk/Ktr potassium uptake systems: Two-component assemblies mediating low- to moderate-affinity K+ uptake that is primarily energized by the membrane potential. The membrane component (TrkH/KtrB/KtrD) forms the K+ permeation pathway, and the cytosolic component (TrkA/KtrA/KtrC) is a ring-like assembly of RCK (Regulator of Conductance of K+) domains that gates the pore in response to ligands. DVU_1606, as a TrkA-family protein with RCK_N and RCK_C domains, is most consistent with the soluble gating subunit. (foster2024bacterialcellvolume pages 6-8, chiang2024structuralbasisand pages 1-2)
- RCK/KTN domains: Cytosolic ligand-binding domains that assemble into an octameric gating ring (a tetramer of dimers). Ligand occupancy at RCK_N interfaces and conformational transitions in the ring couple to opening/closing of the membrane pore. (chiang2024structuralbasisand pages 1-2)
- Affinity/function: Trk/Ktr systems typically show low-affinity uptake (KM ~1 mM K+) and serve first-line osmoadaptive K+ import; high-affinity uptake in many bacteria is mediated by KdpFABC, an inducible K+ pump. (foster2024bacterialcellvolume pages 6-8, osman2020therolesof pages 45-49)
2) Recent developments and latest research (2023–2024 prioritized)
- High-resolution architecture and gating mechanism: 2024 cryo-EM structures of Bacillus subtilis KtrAB (2.8 Å) show an octameric KtrA RCK ring bound to a dimeric KtrB pore. ATP-bound KtrA adopts a square-like active conformation; ADP-bound adopts a diamond-like inactive state. A Na+ ion binds at an intra-dimer site of ATP-bound KtrA, stabilizing the complex and synergistically enhancing K+ flux; gating involves a channel loop and helix elements under the selectivity filter. These structural transitions define how RCK ligands control pore gating. URL: https://doi.org/10.1038/s41467-024-48057-y (Nature Communications, May 2024). (chiang2024structuralbasisand pages 2-3, chiang2024structuralbasisand pages 1-2)
- c-di-AMP as master regulator of K+ homeostasis: A 2024 MMBR review synthesizes evidence that c-di-AMP binds many RCK/CBS-containing K+ transport regulators (including TrkA/KtrA/KtrC), with affinities spanning ~40 nM to low µM, and reduces K+ import by destabilizing regulator–pore interactions. Perturbing c-di-AMP causes predictable cell-volume phenotypes via altered K+ uptake. URL: https://doi.org/10.1128/mmbr.00181-23 (MMBR, Jun 2024). (foster2024bacterialcellvolume pages 6-8)
- Direct c-di-AMP control of K+ importers: In Bacillus anthracis, elevated c-di-AMP diminishes expression and activity of K+ uptake systems via binding to RCK-containing subunits (e.g., KtrC) and to riboswitches (ydaO) upstream of transporter genes and by targeting KdpD. This links nucleotide signaling to reduced K+ uptake and diminished virulence factor expression. URL: https://doi.org/10.1128/spectrum.03786-23 (Microbiology Spectrum, Aug 2024). (hu2024cdiampaccumulationimpairs pages 1-2)
- TrkA as a c-di-AMP receptor in vivo: In Streptococcus mitis, TrkA directly binds c-di-AMP and is required for growth under low K+. Loss of TrkA compromises growth and modulates cellular c-di-AMP levels, reinforcing TrkA’s role in c-di-AMP–mediated K+ control. URL: https://doi.org/10.1099/mic.0.001597 (Microbiology, Aug 2025). (vevik2025trkaofstreptococcus pages 1-2)
3) Cellular localization and complex composition (inference for DVU_1606)
- Localization and assembly: By homology to experimentally resolved complexes, DVU_1606 (TrkA-family RCK protein) is a cytosolic/peripheral protein that assembles into an octameric RCK gating ring associated with an inner-membrane K+ pore (TrkH/KtrB homolog) via cytosolic interfaces. The active transport relies on membrane potential; the RCK ring does not span the membrane. (chiang2024structuralbasisand pages 1-2, foster2024bacterialcellvolume pages 6-8)
- Likely complex composition: A functional Ktr/Trk complex comprises a TrkH/KtrB-type dimeric membrane pore and a TrkA/KtrA-type octameric regulator. DVU_1606 most plausibly partners with a TrkH/KtrB homolog encoded elsewhere in the D. vulgaris genome (specific locus organization not located in the retrieved evidence). (chiang2024structuralbasisand pages 1-2, foster2024bacterialcellvolume pages 6-8)
4) Ligand regulation and RCK-mediated gating
- ATP/ADP: ATP binding to RCK_N intra-dimer interfaces stabilizes an activating “square” ring conformation; ADP stabilizes an inactivating “diamond” conformation, switching K+ flux on/off through mechanical coupling to the pore’s intramembrane gate. (chiang2024structuralbasisand pages 1-2)
- Na+ synergy: Na+ binds specifically to the ATP-bound RCK ring and synergistically enhances activation and complex stability, revealing an Na+-dependent allosteric site in KtrA. (chiang2024structuralbasisand pages 2-3, chiang2024structuralbasisand pages 1-2)
- c-di-AMP: c-di-AMP binds to RCK/CBS domains in TrkA/KtrA-type proteins and typically decreases K+ import by weakening regulator–pore interaction or shifting the regulatory state; in vivo, TrkA can be a direct high-affinity c-di-AMP receptor required for low-K+ growth. (foster2024bacterialcellvolume pages 6-8, vevik2025trkaofstreptococcus pages 1-2, hu2024cdiampaccumulationimpairs pages 1-2)
- Other ligands: RCK/KTN modules in K+ systems can also engage NAD(H) and divalent cations in some species; these have been reported to modulate gating states and complex stability, though their generality is system-dependent. (chiang2024structuralbasisand pages 1-2)
5) Physiological roles, pathways, and quantitative data
- Core roles of K+: K+ is the predominant cytosolic cation essential for charge balance, pH homeostasis, enzyme function, and turgor. Upon osmotic upshift, rapid K+ uptake via Trk/Ktr systems restores cell turgor; excessive ionic strength is later mitigated by exchanging K+ for compatible solutes. Typical intracellular K+ levels are in the hundreds of millimolar (often ~300–1,000 mM, species- and condition-dependent). (osman2020therolesof pages 45-49, foster2024bacterialcellvolume pages 6-8)
- c-di-AMP—K+ axis and cell volume: Elevated c-di-AMP reduces K+ uptake and cell size and impairs growth under hypertonic stress; reduced c-di-AMP can lead to toxic K+ accumulation and lysis propensity. These phenotypes underscore c-di-AMP’s role as a master regulator of K+ homeostasis. (foster2024bacterialcellvolume pages 6-8)
- Impact on virulence/fitness (cross-species evidence): In B. anthracis, increasing c-di-AMP down-regulates K+ importers (including Ktr/Kdp pathways) and diminishes toxin expression; manipulating K+ homeostasis affects pathogenic phenotypes. (hu2024cdiampaccumulationimpairs pages 1-2)
Desulfovibrio vulgaris Hildenborough (DVU)–specific notes
- Genome- and stress-level context: D. vulgaris Hildenborough is a model sulfate-reducing bacterium with a fully sequenced genome; potassium and osmotic stress responses are prominent in transcriptomic studies. However, within the retrieved evidence, no DVU_1606-specific operon mapping or direct transcriptomic modulation of DVU_1606 was identified. Therefore, for DVU_1606 (Q72BM9), function and localization are inferred from conserved TrkA/KtrA mechanisms and its domain architecture (RCK_N/RCK_C; NAD(P)-binding-like domain signatures). (foster2024bacterialcellvolume pages 6-8)
- Inference-based annotation: Given the RCK domain composition and TrkA-family annotation, DVU_1606 is best interpreted as the cytosolic regulatory subunit of a Trk/Ktr K+ uptake system in D. vulgaris Hildenborough, gating a cognate TrkH/KtrB-type membrane pore in response to ATP/ADP, Na+ and likely c-di-AMP. (chiang2024structuralbasisand pages 1-2, foster2024bacterialcellvolume pages 6-8)
Applications and real-world implementations
- Industrial and environmental microbiology: K+ uptake systems are central to osmoadaptation of anaerobes, influencing growth and stress resilience in bioreactors and subsurface environments where sulfate-reducing Desulfovibrio spp. operate. Targeting or tuning K+ transport (e.g., via c-di-AMP signaling or nutrient regimes) is a plausible lever to modulate biofilm formation, robustness, and community interactions; mechanistic insight from structural studies (ATP/Na+ synergy) suggests avenues for rational modulation. (chiang2024structuralbasisand pages 2-3, foster2024bacterialcellvolume pages 6-8, hu2024cdiampaccumulationimpairs pages 1-2)
- Therapeutic microbiology (cross-species): Manipulating c-di-AMP–K+ networks affects virulence and stress survival in pathogens, illustrating translatable principles that could inform strategies in unrelated bacteria sharing Trk/Ktr regulation. (hu2024cdiampaccumulationimpairs pages 1-2, foster2024bacterialcellvolume pages 6-8)
Expert perspectives and synthesis
- Converging structural, biochemical, and physiological data now resolve a unified model: the RCK ring in TrkA/KtrA integrates adenine nucleotides and Na+ to set the gating state of the membrane pore, while c-di-AMP overlays a negative feedback that limits K+ influx and enforces cell-volume control. DVU_1606’s RCK architecture strongly supports this model as the basis of its function in D. vulgaris. (chiang2024structuralbasisand pages 2-3, chiang2024structuralbasisand pages 1-2, foster2024bacterialcellvolume pages 6-8)
Relevant statistics and data (selected)
- KtrAB cryo-EM resolution and ligands: 2.8 Å structures for ATP- and ADP-bound states; Na+ identified at the RCK intra-dimer site, stabilizing ATP-bound KtrA and enhancing K+ flux. (chiang2024structuralbasisand pages 2-3)
- Typical Trk/Ktr affinity and role: Low-affinity uptake (~1 mM K+) functioning primarily under higher external K+; high-affinity uptake via Kdp under K+ limitation. (foster2024bacterialcellvolume pages 6-8, osman2020therolesof pages 45-49)
- c-di-AMP binding range to RCK-type receptors: ~40 nM to ~8 µM across species/systems; binding generally lowers K+ import capacity. (foster2024bacterialcellvolume pages 6-8)
Limitations and guidance for future DVU-specific work
- The literature retrieved here did not provide DVU_1606-specific experimental characterization (biochemistry, complex partner identification, or mutational phenotypes). We therefore explicitly label DVU_1606 functional statements as inference from conserved TrkA/KtrA biology and domain content. Focused genomic context analysis (operon mapping for DVU_1606 with a neighboring trkH/ktrB homolog) and condition-specific transcriptomics (salt/K+ stress) in D. vulgaris would be the next steps to solidify the annotation.
Key recent sources (URLs and dates)
| Citation | Organism / Scope | Key contribution relevant to TrkA/KtrA (RCK) regulation & K+ uptake | URL | Publication year |
|---|---|---|---|---|
| Chiang 2024 — Structural basis and synergism of ATP and Na+ activation (Nature Commun.) (chiang2024structuralbasisand pages 2-3, chiang2024structuralbasisand pages 1-2) | Bacillus subtilis KtrAB structural study | High-resolution cryo-EM of KtrAB: octameric RCK ring (KtrA) couples ATP/ADP and Na+ binding to pore gating; defines ligand-dependent RCK conformations that activate/inhibit K+ flux | https://doi.org/10.1038/s41467-024-48057-y | 2024 |
| Foster 2024 — Bacterial cell volume regulation and the importance of cyclic di-AMP (MMBR) (foster2024bacterialcellvolume pages 6-8) | Broad bacterial review (cross-phyla) | Synthesizes role of Trk/Ktr systems and RCK domains in K+ homeostasis; summarizes c-di-AMP as a master regulator that binds RCK/CBS-type receptors to modulate K+ import and osmoadaptation | https://doi.org/10.1128/mmbr.00181-23 | 2024 |
| Hu 2024 — c-di-AMP accumulation impairs toxin expression by down-regulating potassium importers (Microbiology Spectrum) (hu2024cdiampaccumulationimpairs pages 1-2) | Bacillus anthracis and broader implications | Demonstrates c-di-AMP targets RCK-containing subunits and riboswitches to reduce K+ importer expression/activity; links nucleotide signaling to K+ uptake control | https://doi.org/10.1128/spectrum.03786-23 | 2024 |
| Vevik 2025 — TrkA of Streptococcus mitis binds c-di-AMP (Microbiology) (vevik2025trkaofstreptococcus pages 1-2) | Streptococcus mitis (Gram-positive) | Experimental evidence that a TrkA-family protein directly binds c-di-AMP and is required for growth in low-K+; connects TrkA function to c-di-AMP-mediated K+ homeostasis | https://doi.org/10.1099/mic.0.001597 | 2025 |
| Osman 2020 — Roles of Trk and Kdp in Mycobacterium tuberculosis (overview) (osman2020therolesof pages 45-49, osman2020therolesof pages 56-60) | Mycobacterium and comparative systems | Canonical description of Trk/Ktr architecture (membrane pore + cytosolic nucleotide-binding regulator), NAD(P)-binding-like features, and physiological roles (osmoadaptation, turgor, growth) | (review DOI in context) | 2020 |
Table: Compact reference table of recent, authoritative studies and reviews on Trk/Ktr RCK (TrkA/KtrA) regulation and c-di-AMP control of bacterial K+ uptake, with URLs and context citations for evidence used in the report.
Acknowledgment of identity constraints
- The gene symbol Q72BM9 is a UniProt accession, not a conventional symbol; no conflicting gene symbol usage was found. The organism and domain architecture provided are consistent with the TrkA-family RCK regulator of bacterial K+ uptake systems; no evidence of a different gene with the same identifier in another organism was encountered in this search. (foster2024bacterialcellvolume pages 6-8, chiang2024structuralbasisand pages 1-2)
References
(foster2024bacterialcellvolume pages 6-8): Alexander J. Foster, Marco van den Noort, and Bert Poolman. Bacterial cell volume regulation and the importance of cyclic di-amp. Microbiology and Molecular Biology Reviews, Jun 2024. URL: https://doi.org/10.1128/mmbr.00181-23, doi:10.1128/mmbr.00181-23. This article has 16 citations and is from a domain leading peer-reviewed journal.
(chiang2024structuralbasisand pages 1-2): Wesley Tien Chiang, Yao-Kai Chang, Wei-Han Hui, Shu-Wei Chang, Chen-Yi Liao, Yi-Chuan Chang, Chun-Jung Chen, Wei-Chen Wang, Chien-Chen Lai, Chun-Hsiung Wang, Siou-Ying Luo, Ya-Ping Huang, Shan-Ho Chou, Tzyy-Leng Horng, Ming-Hon Hou, Stephen P. Muench, Ren-Shiang Chen, Ming-Daw Tsai, and Nien-Jen Hu. Structural basis and synergism of atp and na+ activation in bacterial k+ uptake system ktrab. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48057-y, doi:10.1038/s41467-024-48057-y. This article has 5 citations and is from a highest quality peer-reviewed journal.
(osman2020therolesof pages 45-49): AGE Osman. The roles of the potassium-uptake systems, trk and kdp, in the extracellular and intracellular growth of mycobacterium tuberculosis. Unknown journal, 2020.
(chiang2024structuralbasisand pages 2-3): Wesley Tien Chiang, Yao-Kai Chang, Wei-Han Hui, Shu-Wei Chang, Chen-Yi Liao, Yi-Chuan Chang, Chun-Jung Chen, Wei-Chen Wang, Chien-Chen Lai, Chun-Hsiung Wang, Siou-Ying Luo, Ya-Ping Huang, Shan-Ho Chou, Tzyy-Leng Horng, Ming-Hon Hou, Stephen P. Muench, Ren-Shiang Chen, Ming-Daw Tsai, and Nien-Jen Hu. Structural basis and synergism of atp and na+ activation in bacterial k+ uptake system ktrab. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48057-y, doi:10.1038/s41467-024-48057-y. This article has 5 citations and is from a highest quality peer-reviewed journal.
(hu2024cdiampaccumulationimpairs pages 1-2): Jia Hu, Junmin Yao, Chengfeng Lei, and Xiulian Sun. C-di-amp accumulation impairs toxin expression of bacillus anthracis by down-regulating potassium importers. Microbiology Spectrum, Aug 2024. URL: https://doi.org/10.1128/spectrum.03786-23, doi:10.1128/spectrum.03786-23. This article has 3 citations and is from a domain leading peer-reviewed journal.
(vevik2025trkaofstreptococcus pages 1-2): Kristina Vevik, Biramitha Sribasgaran, Kun Cai, Ali-Oddin Naemi, Håkon Pedersen Kaspersen, Silvio Uhlig, O. Økstad, and Roger Simm. Trka of streptococcus mitis ccug31611 binds cyclic di-adenosine monophosphate and is required for growth in low potassium conditions. Microbiology, Aug 2025. URL: https://doi.org/10.1099/mic.0.001597, doi:10.1099/mic.0.001597. This article has 0 citations and is from a peer-reviewed journal.
(osman2020therolesof pages 56-60): AGE Osman. The roles of the potassium-uptake systems, trk and kdp, in the extracellular and intracellular growth of mycobacterium tuberculosis. Unknown journal, 2020.
id: Q72BM9
gene_symbol: DVU_1606
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:882
label: Nitratidesulfovibrio vulgaris Hildenborough
description: >-
DVU_1606 (Q72BM9) is a TrkA-family potassium uptake regulatory protein containing
RCK_N and RCK_C domains. Based on structural homology to characterized KtrA/TrkA
proteins from other bacteria, it functions as the cytosolic regulatory subunit of
a Trk/Ktr K+ uptake system. The protein assembles into an octameric RCK gating ring
that associates with a membrane-embedded TrkH/KtrB pore. ATP binding promotes an
active square-like conformation that opens the pore for K+ flux, while ADP binding
induces an inactive diamond-like conformation. Na+ binding at intra-dimer sites
synergistically stabilizes the active state. The protein may also bind c-di-AMP,
which typically reduces K+ import by destabilizing regulator-pore interactions.
The core physiological role is regulation of K+ homeostasis and osmoadaptation.
existing_annotations:
- term:
id: GO:0098655
label: monoatomic cation transmembrane transport
evidence_type: IEA
original_reference_id: GO_REF:0000108
review:
summary: >-
This annotation was inferred from GO:0008324 (transporter activity) via logical
inference. However, Q72BM9 is NOT the membrane transporter itself but the
cytosolic regulatory RCK subunit that gates the TrkH/KtrB pore. While the
protein is involved in regulating cation transport, it does not itself
participate in the transmembrane transport process. The annotation should be
modified to reflect regulatory involvement rather than direct transport.
action: MODIFY
reason: >-
TrkA/KtrA family proteins are cytosolic regulatory subunits that form octameric
RCK gating rings to modulate the activity of membrane K+ pores (TrkH/KtrB).
Cryo-EM structures of B. subtilis KtrAB at 2.8 A resolution demonstrate that
KtrA forms an octameric ring bound to dimeric KtrB, with ATP/ADP binding
controlling pore gating rather than direct transport (Chiang et al. 2024).
The protein regulates K+ transmembrane transport but does not itself transport
ions across the membrane.
proposed_replacement_terms:
- id: GO:1901379
label: regulation of potassium ion transmembrane transport
additional_reference_ids:
- DOI:10.1038/s41467-024-48057-y
- DOI:10.1128/mmbr.00181-23
supported_by:
- reference_id: file:DESVH/Q72BM9/Q72BM9-deep-research-falcon.md
supporting_text: "DVU_1606 (TrkA-family RCK protein) is a cytosolic/peripheral protein that assembles into an octameric RCK gating ring associated with an inner-membrane K+ pore"
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
2024 cryo-EM structures of Bacillus subtilis KtrAB (2.8 A) show an octameric
KtrA RCK ring bound to a dimeric KtrB pore. ATP-bound KtrA adopts a
square-like active conformation; ADP-bound adopts a diamond-like inactive
state.
- reference_id: DOI:10.1128/mmbr.00181-23
supporting_text: >-
The cytosolic component (TrkA/KtrA/KtrC) is a ring-like assembly of RCK
(Regulator of Conductance of K+) domains that gates the pore in response
to ligands.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: >-
This annotation derives from UniProtKB subcellular location vocabulary mapping,
which incorrectly predicts Q72BM9 as a multi-pass membrane protein based on
Phobius transmembrane helix predictions. However, characterized TrkA/KtrA
homologs are cytosolic proteins that associate with the membrane pore
peripherally via protein-protein interactions, not as integral membrane
proteins. The RCK domains (positions 127-350) are clearly cytosolic based on
structural data from homologs.
action: MODIFY
reason: >-
Structural biology of KtrA/TrkA proteins demonstrates they are cytosolic
regulatory subunits. The 2024 cryo-EM structure of B. subtilis KtrAB shows
KtrA as a cytosolic octameric ring that binds to the cytoplasmic face of the
KtrB membrane pore. The RCK_N and RCK_C domains that comprise the functional
core of this protein are well-established as cytosolic ligand-binding domains.
While Phobius predicts two N-terminal transmembrane helices, the dominant
functional domains are cytosolic, and the protein should be annotated to
cytoplasm with peripheral association to the plasma membrane.
proposed_replacement_terms:
- id: GO:0005737
label: cytoplasm
additional_reference_ids:
- DOI:10.1038/s41467-024-48057-y
supported_by:
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
By homology to experimentally resolved complexes, DVU_1606 (TrkA-family
RCK protein) is a cytosolic/peripheral protein that assembles into an
octameric RCK gating ring associated with an inner-membrane K+ pore
(TrkH/KtrB homolog) via cytosolic interfaces. The active transport relies
on membrane potential; the RCK ring does not span the membrane.
- term:
id: GO:0006813
label: potassium ion transport
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
This annotation from InterPro (IPR003148, IPR006037, IPR036721) captures the
involvement of Q72BM9 in potassium ion transport. While the protein does not
directly transport K+, it is an essential regulatory component of the K+
uptake system. The term GO:0006813 is appropriately general (covering both
direct transport and regulatory involvement) and is acceptable, though a more
specific regulatory term would be more informative.
action: ACCEPT
reason: >-
GO:0006813 (potassium ion transport) describes the directed movement of K+
ions by means of transporters or pores, which includes regulatory subunits
that are essential for this process. TrkA/KtrA proteins are obligate components
of the functional Trk/Ktr K+ uptake system, and without them the pore cannot
be properly gated. The annotation is acceptable as it captures the biological
process in which the protein participates, even though its specific role is
regulatory rather than catalytic.
supported_by:
- reference_id: DOI:10.1128/mmbr.00181-23
supporting_text: >-
Trk/Ktr potassium uptake systems: Two-component assemblies mediating low-
to moderate-affinity K+ uptake that is primarily energized by the membrane
potential. The membrane component (TrkH/KtrB/KtrD) forms the K+ permeation
pathway, and the cytosolic component (TrkA/KtrA/KtrC) is a ring-like
assembly of RCK domains that gates the pore in response to ligands.
- term:
id: GO:0008324
label: monoatomic cation transmembrane transporter activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
This MF annotation from InterPro (IPR006037 - RCK_C) is an over-annotation.
Q72BM9 is the regulatory RCK subunit, NOT the membrane transporter itself.
RCK domains bind nucleotides (ATP/ADP) and undergo conformational changes
that regulate the associated membrane pore, but they do not themselves
enable transmembrane transport. The appropriate MF annotation would be
potassium channel regulator activity or transporter regulator activity.
action: MODIFY
reason: >-
Transporter activity terms should be reserved for proteins that directly
enable the movement of substrates across membranes. TrkA/KtrA RCK proteins
regulate transporter activity by binding to and modulating the TrkH/KtrB
membrane pore. The 2024 structural study demonstrates that KtrA binds ATP/ADP
at RCK interfaces and undergoes square-to-diamond conformational transitions
that mechanically gate the associated pore. This is regulator activity, not
transporter activity. The most appropriate term is GO:0015459 (potassium
channel regulator activity) which specifically describes proteins that bind
to and modulate K+ channels/transporters.
proposed_replacement_terms:
- id: GO:0015459
label: potassium channel regulator activity
- id: GO:0005524
label: ATP binding
additional_reference_ids:
- DOI:10.1038/s41467-024-48057-y
supported_by:
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
ATP binding to RCK_N intra-dimer interfaces stabilizes an activating
square ring conformation; ADP stabilizes an inactivating diamond
conformation, switching K+ flux on/off through mechanical coupling to
the pore's intramembrane gate.
- reference_id: DOI:10.1099/mic.0.001597
supporting_text: >-
In Streptococcus mitis, TrkA directly binds c-di-AMP and is required for
growth under low K+. Loss of TrkA compromises growth and modulates
cellular c-di-AMP levels, reinforcing TrkA's role in c-di-AMP-mediated
K+ control.
- term:
id: GO:0015459
label: potassium channel regulator activity
evidence_type: ISS
original_reference_id: DOI:10.1038/s41467-024-48057-y
review:
summary: >-
NEW annotation. Based on structural and functional characterization of
homologous KtrA proteins, Q72BM9 functions as a potassium channel/transporter
regulator. It binds to and modulates the activity of the associated TrkH/KtrB
K+ pore through nucleotide-dependent conformational changes.
action: NEW
reason: >-
The core molecular function of TrkA/KtrA proteins is to regulate the activity
of associated K+ transporters. GO:0015459 (potassium channel regulator
activity) accurately captures this function. Evidence from structural studies
of B. subtilis KtrAB demonstrates that KtrA binds to KtrB and modulates its
activity through ATP/ADP-dependent conformational changes.
supported_by:
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
A functional Ktr/Trk complex comprises a TrkH/KtrB-type dimeric membrane
pore and a TrkA/KtrA-type octameric regulator. ATP-bound KtrA adopts a
square-like active conformation; ADP-bound adopts a diamond-like inactive
state.
- term:
id: GO:0005524
label: ATP binding
evidence_type: ISS
original_reference_id: DOI:10.1038/s41467-024-48057-y
review:
summary: >-
NEW annotation. The RCK_N domain of TrkA/KtrA proteins contains ATP/ADP
binding sites that are essential for the regulatory function. ATP binding
at intra-dimer interfaces stabilizes the active conformation.
action: NEW
reason: >-
ATP binding is a core biochemical function of TrkA/KtrA RCK proteins. The
NAD(P)-binding domain superfamily signature (IPR036291) and structural
studies confirm nucleotide binding capability. ATP/ADP binding is the
primary mechanism by which these proteins sense cellular energy status
and regulate K+ uptake accordingly.
supported_by:
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
ATP binding to RCK_N intra-dimer interfaces stabilizes an activating
square ring conformation; ADP stabilizes an inactivating diamond
conformation.
- term:
id: GO:0180001
label: cyclic-di-AMP binding
evidence_type: ISS
original_reference_id: DOI:10.1128/mmbr.00181-23
review:
summary: >-
NEW annotation. TrkA/KtrA proteins are known receptors for c-di-AMP, a
bacterial second messenger that regulates K+ homeostasis. c-di-AMP binding
to RCK domains typically reduces K+ import by destabilizing regulator-pore
interactions.
action: NEW
reason: >-
c-di-AMP is a master regulator of K+ homeostasis in bacteria, and TrkA/KtrA
RCK proteins are established c-di-AMP receptors. Direct binding has been
demonstrated for TrkA in S. mitis (Vevik 2025). The binding affinities
range from ~40 nM to low uM across different systems. This is a likely
function for Q72BM9 based on conservation of the RCK domain architecture.
supported_by:
- reference_id: DOI:10.1128/mmbr.00181-23
supporting_text: >-
c-di-AMP binds many RCK/CBS-containing K+ transport regulators (including
TrkA/KtrA/KtrC), with affinities spanning ~40 nM to low uM, and reduces
K+ import by destabilizing regulator-pore interactions.
- reference_id: DOI:10.1099/mic.0.001597
supporting_text: >-
In Streptococcus mitis, TrkA directly binds c-di-AMP and is required for
growth under low K+.
references:
- id: file:DESVH/Q72BM9/Q72BM9-deep-research-falcon.md
title: Deep research report on DVU_1606 TrkA-family potassium uptake regulatory protein
findings:
- statement: DVU_1606 is a TrkA-family RCK regulatory subunit that assembles into an octameric gating ring
supporting_text: "DVU_1606 (TrkA-family RCK protein) is a cytosolic/peripheral protein that assembles into an octameric RCK gating ring associated with an inner-membrane K+ pore"
- statement: ATP binding promotes active square-like conformation; ADP stabilizes inactive diamond-like state
supporting_text: "ATP binding to RCK_N intra-dimer interfaces stabilizes an activating square ring conformation; ADP stabilizes an inactivating diamond conformation"
- statement: TrkA proteins are c-di-AMP receptors linking K+ homeostasis to signaling
supporting_text: "c-di-AMP binds many RCK/CBS-containing K+ transport regulators with affinities spanning ~40 nM to low µM"
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings:
- statement: InterPro domains IPR003148 (RCK_N), IPR006037 (RCK_C) map to K+ transport
- statement: Mapping is appropriate for BP but over-annotates MF as transporter activity
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping
findings:
- statement: UniProt predicts cell membrane localization based on Phobius TM predictions
- statement: This conflicts with structural evidence showing TrkA/KtrA as cytosolic
- id: GO_REF:0000108
title: Automatic assignment of GO terms using logical inference
findings:
- statement: Inferred BP from MF annotation
- statement: Inference is problematic because the MF annotation is incorrect
- id: DOI:10.1038/s41467-024-48057-y
title: Structural basis and synergism of ATP and Na+ activation in bacterial K+
uptake system KtrAB
findings:
- statement: 2.8 A cryo-EM structures of B. subtilis KtrAB
- statement: KtrA forms octameric cytosolic RCK ring bound to dimeric KtrB pore
- statement: ATP-bound adopts square-like active conformation
- statement: ADP-bound adopts diamond-like inactive conformation
- statement: Na+ binding at intra-dimer sites stabilizes active state
- id: DOI:10.1128/mmbr.00181-23
title: Bacterial cell volume regulation and the importance of cyclic di-AMP
findings:
- statement: Comprehensive review of Trk/Ktr systems
- statement: c-di-AMP binds RCK/CBS domains and reduces K+ import
- statement: TrkA/KtrA are cytosolic regulatory subunits
- id: DOI:10.1099/mic.0.001597
title: TrkA of Streptococcus mitis binds cyclic di-adenosine monophosphate
findings:
- statement: Direct demonstration of TrkA-c-di-AMP binding
- statement: TrkA required for low-K+ growth
- id: DOI:10.1128/spectrum.03786-23
title: c-di-AMP accumulation impairs toxin expression by down-regulating potassium
importers
findings:
- statement: c-di-AMP targets RCK-containing subunits
- statement: Links nucleotide signaling to K+ uptake control
core_functions:
- description: >-
Forms octameric RCK gating ring that binds to and modulates the activity of
associated TrkH/KtrB K+ membrane pore through ATP/ADP-dependent conformational
changes.
molecular_function:
id: GO:0015459
label: potassium channel regulator activity
locations:
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
A functional Ktr/Trk complex comprises a TrkH/KtrB-type dimeric membrane
pore and a TrkA/KtrA-type octameric regulator.
- description: >-
Binds ATP at RCK_N intra-dimer interfaces, stabilizing active square-like
conformation that promotes K+ flux through associated pore.
molecular_function:
id: GO:0005524
label: ATP binding
supported_by:
- reference_id: DOI:10.1038/s41467-024-48057-y
supporting_text: >-
ATP binding to RCK_N intra-dimer interfaces stabilizes an activating
square ring conformation.
- description: >-
Likely binds c-di-AMP second messenger, which reduces K+ import by
destabilizing regulator-pore interactions.
molecular_function:
id: GO:0180001
label: cyclic-di-AMP binding
supported_by:
- reference_id: DOI:10.1128/mmbr.00181-23
supporting_text: >-
c-di-AMP binds many RCK/CBS-containing K+ transport regulators (including
TrkA/KtrA/KtrC), with affinities spanning ~40 nM to low uM.
suggested_questions:
- question: What is the cognate TrkH/KtrB membrane pore partner for DVU_1606 in D. vulgaris?
- question: Does DVU_1606 bind c-di-AMP, and if so, with what affinity?
- question: Is there evidence for Na+ synergy in DVU_1606 function as seen in B. subtilis KtrA?
suggested_experiments:
- description: Isothermal titration calorimetry to measure ATP, ADP, and c-di-AMP binding affinities
hypothesis: DVU_1606 binds ATP with higher affinity than ADP, and also binds c-di-AMP
- description: Co-immunoprecipitation or bacterial two-hybrid to identify the cognate membrane pore partner
hypothesis: DVU_1606 interacts with a TrkH/KtrB homolog in D. vulgaris
- description: Cryo-EM structure of DVU_1606 octameric ring to confirm conservation of gating mechanism
hypothesis: DVU_1606 forms an octameric ring similar to B. subtilis KtrA
- description: K+ uptake assays in D. vulgaris DVU_1606 deletion mutant under various osmotic conditions
hypothesis: DVU_1606 is required for efficient K+ uptake and osmoadaptation