Bacterial TonB-energized outer-membrane ferric-siderophore import

A conserved Gram-negative bacterial transport module mediating active import of ferric-siderophore complexes across the outer membrane into the periplasm. Because the outer membrane lacks an electrochemical proton gradient, outer-membrane TonB-dependent ferric-siderophore receptors (such as BfrD1) rely on the inner-membrane TonB-ExbB-ExbD complex — comprising the pentameric ExbB proton-channel stator (ExbB4), the dimeric ExbD proton-coupling subunit (ExbD5), and the inner-membrane-anchored, periplasm-spanning energy transducer TonB — to harvest and transduce the cytoplasmic-membrane proton-motive force across the periplasmic space. Physical contact between the C-terminal domain of TonB and the N-terminal TonB box of the receptor plug domain drives conformational opening of the 22-stranded outer-membrane beta-barrel channel and translocation of the ferric-siderophore complex into the periplasm. Siderophore biosynthesis, extracellular siderophore secretion, and subsequent periplasmic-to-cytoplasmic ABC transport are outside this module boundary.

MODULE:bacterial_tonb_siderophore_importDRAFTBiological Processmodules/bacterial_tonb_siderophore_import.yaml
siderophore-iron import into cellGO:0033214
GO:0033214
siderophore-iron import into cell
GO:0033214 provides the biological-process context for receptor-mediated import of ferric-siderophore complexes into the bacterial cell.
GO:0031992
energy transducer activity
GO:0031992 defines the proton-motive-force energy transduction activity of TonB that powers active outer-membrane transport.
PMID:20420522
TonB-dependent transporters: regulation, structure, and function.
Establishes the conserved structural and mechanistic model of TonB-dependent outer-membrane transporters (22-stranded beta-barrel with an N-terminal luminal plug domain and TonB box) energized by the inner-membrane TonB-ExbB-ExbD proton-motive-force transducing complex.
TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that bind and transport ferric chelates, called siderophores, as well as vitamin B(12), nickel complexes, and carbohydrates. The transport process requires energy in the form of proton motive force and a complex of three inner membrane proteins, TonB-ExbB-ExbD, to transduce this energy to the outer membrane.
PMID:37219427
Energization of Outer Membrane Transport by the ExbB ExbD Molecular Motor.
Establishes that ExbB forms a pentameric inner-membrane pore enclosing an ExbD dimer that harvests the cytoplasmic-membrane proton-motive force and transmits mechanical energy to TonB.
ExbB forms a pentamer with a pore inside, in which an ExbD dimer resides. This complex harvests the energy of the pmf and transmits it to TonB.
PMID:26412281
An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.
Demonstrates that Variovorax paradoxus S110 and P4B biosynthesize vacidobactin A/B and variobactin A/B nonribosomal peptide-polyketide siderophore natural products.
Isolation of these indicated metabolites provided the novel compounds vacidobactin A and B, which are methylmalonate-incorporating acidobactins and represent the first natural products isolated from Variovorax (Fig. 2a, Supplementary Figs 12c, 13–16 and Supplementary Table 5).
file:VARPD/exbB4/exbB4-ai-review.yaml
Variovorax paradoxus exbB4 gene review
A0A0H2MHH3 (VPARA_25810) encodes the 238-residue inner-membrane ExbB4 proton-channel stator subunit in the exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) cluster.
Biopolymer transport protein ExbB4 (VPARA_25810) in Variovorax paradoxus strain TBEA6 is a 238-amino-acid integral inner-membrane multi-pass protein containing three transmembrane alpha-helices (residues 20-41, 127-150, and 174-195) and a conserved MotA/TolQ/ExbB proton-channel domain (Pfam PF01618, InterPro IPR002898, PANTHER PTHR30625:SF14, residues 100-201). Encoded in the syntenic exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) siderophore-uptake gene cluster, ExbB4 assembles with ExbD5 (VPARA_25800) and TonB (VPARA_25820) into the plasma-membrane TonB-ExbB-ExbD energy-transducing complex, where the ExbB pentamer forms the proton-conducting transmembrane stator that harvests the cytoplasmic-membrane proton-motive force and transmits mechanical energy through TonB to outer-membrane TonB-dependent ferric-siderophore receptors such as BfrD1 (VPARA_25830).
file:VARPD/exbD5/exbD5-ai-review.yaml
Variovorax paradoxus exbD5 gene review
A0A0H2M1F3 (VPARA_25800) encodes the 137-residue inner-membrane ExbD5 proton-coupling subunit containing the conserved transmembrane Asp23 residue in the exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) cluster.
Biopolymer transport protein ExbD5 (VPARA_25800) in Variovorax paradoxus strain TBEA6 is a 137-amino-acid inner-membrane type II single-pass protein (Pfam PF02472, InterPro IPR003400, PANTHER PTHR30558) containing an N-terminal transmembrane alpha-helix (residues 20-39) with the invariant proton-binding aspartate residue Asp23 (within 20-PLVDVMLVLLIIFIITVPVM-39) and a C-terminal periplasmic domain (residues 40-137). Encoded at the 5' end of the syntenic exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) ferric-siderophore uptake cluster, ExbD5 forms a central transmembrane dimer inside the inner-membrane ExbB4 pentamer pore, coupling proton translocation via Asp23 to periplasmic conformational changes that energize TonB (VPARA_25820) and drive active outer-membrane ferric-siderophore import through BfrD1 (VPARA_25830).
file:VARPD/tonB/tonB-ai-review.yaml
Variovorax paradoxus tonB gene review
A0A0H2M2E3 (VPARA_25820) encodes the 232-residue inner-membrane-anchored, periplasm-spanning TonB energy transducer encoded in the exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) cluster.
TonB (VPARA_25820) is a 232-amino-acid inner-membrane proton-motive-force energy transducer in Variovorax paradoxus TBEA6 encoded in the conserved exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) locus immediately upstream of the outer-membrane TonB-dependent ferric-siderophore receptor bfrD1 (VPARA_25830).
file:VARPD/bfrD1/bfrD1-ai-review.yaml
Variovorax paradoxus bfrD1 gene review
A0A0H2M677 (VPARA_25830) encodes the 739-residue outer-membrane TonB-dependent ferric-siderophore receptor BfrD1 co-localized immediately downstream of tonB (VPARA_25820).
BfrD1 (VPARA_25830) is a 739-amino-acid outer-membrane TonB-dependent ferric-siderophore receptor in Variovorax paradoxus TBEA6 encoded immediately downstream of the inner-membrane energy transducer tonB (VPARA_25820).
file:VARPD/fur1/fur1-ai-review.yaml
Variovorax paradoxus fur1 gene review
A0A0H2M8T9 (VPARA_18200) encodes the 139-residue Fur1 ferric uptake transcriptional repressor that regulates expression of siderophore biosynthesis and TonB-dependent ferric-siderophore import genes in response to intracellular Fe(2+).
Under iron-replete conditions, Fe(2+)-loaded holo-Fur1 binds conserved Fur-box operator sequences in target promoters and acts as a transcriptional repressor of iron-acquisition and siderophore biosynthesis/import genes, whereas iron limitation demetallates the regulatory site and derepresses siderophore-mediated iron uptake.
file:PSEPK/tonB/tonB-ai-review.yaml
Pseudomonas putida KT2440 tonB gene review
Q88C75 (PP_5308) encodes the Pseudomonas putida KT2440 TonB energy transducer that powers outer-membrane TonB-dependent siderophore receptors.
Together with its partner proteins ExbB and ExbD, it forms the TonB-ExbB-ExbD complex that harnesses the proton-motive force of the inner membrane and transmits this energy across the periplasm to TonB-dependent transporters (TBDTs) in the outer membrane.
4Nodes
3Parts
0Variant Sets
0Variants
4Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bacterial_tonb_siderophore_import deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

5 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (9 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
exbb_proton_channel_activity exbB (Variovorax paradoxus exbB4)
UniProtKB:A0A0H2MHH3
Family Representative 		proton transmembrane transporter activity
GO:0015078 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
exbd_proton_coupling_activity exbD (Variovorax paradoxus exbD5)
UniProtKB:A0A0H2M1F3
Family Representative 		proton transmembrane transporter activity
GO:0015078 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tonb_transducer_activity tonB (Variovorax paradoxus)
UniProtKB:A0A0H2M2E3
Family Representative 		energy transducer activity
GO:0031992 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tonb_transducer_activity tonB (Pseudomonas putida KT2440)
UniProtKB:Q88C75
Family Representative 		energy transducer activity
GO:0031992 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bfrd1_siderophore_receptor_activity bfrD1 (Variovorax paradoxus)
UniProtKB:A0A0H2M677
Family Representative 		siderophore uptake transmembrane transporter activity
GO:0015344 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
exbb_proton_channel_activity bacterial ExbB inner-membrane proton-channel stator proteins
Family 		proton transmembrane transporter activity
GO:0015078 		Family Id Missing
The family has no identifier linking it to a curated family review.
exbd_proton_coupling_activity bacterial ExbD inner-membrane proton-coupling proteins
Family 		proton transmembrane transporter activity
GO:0015078 		Family Id Missing
The family has no identifier linking it to a curated family review.
tonb_transducer_activity bacterial TonB periplasm-spanning energy transducers
Family 		energy transducer activity
GO:0031992 		Family Id Missing
The family has no identifier linking it to a curated family review.
bfrd1_siderophore_receptor_activity outer-membrane TonB-dependent ferric-siderophore receptors
Family 		siderophore uptake transmembrane transporter activity
GO:0015344 		Family Id Missing
The family has no identifier linking it to a curated family review.

Gene-review completeness (5/5 grounded genes reviewed)

5 complete review(s) · 1 with deep research · 0 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
bfrD1 A0A0H2M677 ✓ ✓ ✗
exbB4 A0A0H2MHH3 ✓ ✓ ✗
exbD5 A0A0H2M1F3 ✓ ✓ ✗
tonB A0A0H2M2E3 ✓ ✓ ✗
tonB Q88C75 ✓ ✓ ✓

Details

Context
BacteriaNCBITaxon:2
Bacterial TonB-energized outer-membrane ferric-siderophore importBiological Processbacterial_tonb_siderophore_import
siderophore-iron import into cellGO:0033214
Context
BacteriaNCBITaxon:2

Models the conserved three-part Gram-negative TonB-ExbB-ExbD-energized outer-membrane ferric-siderophore uptake mechanism (PMID:20420522; PMID:37219427), typed at the top level as BIOLOGICAL_PROCESS because it spans three coupled cell-envelope steps (inner-membrane ExbB4-ExbD5 proton translocation, periplasmic TonB energy transduction, and outer-membrane BfrD1 ferric-siderophore import, the last of which is typed TRANSPORT_STEP). Anchored by the complete four-gene Variovorax paradoxus exbD5-exbB4-tonB-bfrD1 (VPARA_25800-VPARA_25830) locus — ExbD5 (A0A0H2M1F3), ExbB4 (A0A0H2MHH3), TonB (A0A0H2M2E3), and BfrD1 (A0A0H2M677) — together with the reviewed Pseudomonas putida KT2440 TonB exemplar (Q88C75, PP_5308). Because the InterPro domain entries on ExbB/ExbD (IPR002898, IPR003400), TonB (IPR006260, IPR036942), and TonB-dependent receptors (IPR000531, IPR012910, IPR010105) also span TolQ/TolR/MotA/MotB motors and receptors for vitamin B12, heme, nickel chelates, and carbohydrates, family selectors use descriptive preferred_term labels anchored by the curated representative members rather than broad superfamily accessions.

Connections

Proton translocation down the cytoplasmic-membrane proton-motive force through the pentameric ExbB4 pore and dimeric ExbD5 Asp23 rotor drives conformational energization of TonB in the periplasm.
TonB transduces the inner-membrane proton-motive force across the periplasm and physically engages the N-terminal TonB box of the outer-membrane receptor plug domain, driving conformational unplugging and ferric-siderophore translocation across the outer membrane.
Part 1: inner-membrane proton-motive-force harvesting by the ExbB-ExbD proton-channel motor
ExbB-ExbD inner-membrane proton translocation motorTransport Stepexbb_exbd_proton_motor_step

Annotons

ExbB inner-membrane pentameric proton-channel stator
exbb_proton_channel_activity
Participant: Family: bacterial ExbB inner-membrane proton-channel stator proteins
Family:
bacterial ExbB inner-membrane proton-channel stator proteins
Representative Members: exbB (Variovorax paradoxus exbB4)UniProtKB:A0A0H2MHH3

Function

proton transmembrane transporter activityGO:0015078

Processes

proton transmembrane transportGO:1902600 siderophore transportGO:0015891

Locations

plasma membraneGO:0005886

Forms the pentameric three-TM-helix inner-membrane pore housing the ExbD dimer and conducts protons across the cytoplasmic membrane to harvest the proton-motive force.

ExbD inner-membrane proton-coupling rotor subunit
exbd_proton_coupling_activity
Participant: Family: bacterial ExbD inner-membrane proton-coupling proteins
Family:
bacterial ExbD inner-membrane proton-coupling proteins
Representative Members: exbD (Variovorax paradoxus exbD5)UniProtKB:A0A0H2M1F3

Function

proton transmembrane transporter activityGO:0015078

Processes

proton transmembrane transportGO:1902600 siderophore transportGO:0015891

Locations

plasma membraneGO:0005886 outer membrane-bounded periplasmic spaceGO:0030288

Resides as a transmembrane homodimer within the central pore of the ExbB pentamer and uses its conserved transmembrane aspartate (Asp23) to couple proton translocation to periplasmic conformational energization of TonB.

Part 2: inner-membrane proton-motive-force energy transduction across the periplasm by TonB
TonB inner-membrane-to-outer-membrane energy transductionReactiontonb_energy_transduction_step

Annotons

TonB proton-motive-force energy transducer
tonb_transducer_activity
Participant: Family: bacterial TonB periplasm-spanning energy transducers
Family:
bacterial TonB periplasm-spanning energy transducers
Representative Members: tonB (Variovorax paradoxus)UniProtKB:A0A0H2M2E3 tonB (Pseudomonas putida KT2440)UniProtKB:Q88C75

Function

energy transducer activityGO:0031992

Processes

siderophore transportGO:0015891

Locations

plasma membraneGO:0005886 outer membrane-bounded periplasmic spaceGO:0030288

Anchored in the inner membrane via an N-terminal transmembrane helix within the TonB-ExbB-ExbD complex, TonB spans the periplasm via a proline-rich linker so its C-terminal domain can engage the TonB box of outer-membrane ferric-siderophore receptors and transduce proton-motive-force energy.

Part 3: outer-membrane TonB-dependent translocation of ferric-siderophore complexes into the periplasm
Outer-membrane TonB-dependent ferric-siderophore importTransport Steptbdt_siderophore_import_step

Annotons

TonB-dependent outer-membrane ferric-siderophore receptor
bfrd1_siderophore_receptor_activity
Participant: Family: outer-membrane TonB-dependent ferric-siderophore receptors
Family:
outer-membrane TonB-dependent ferric-siderophore receptors
Representative Members: bfrD1 (Variovorax paradoxus)UniProtKB:A0A0H2M677

Function

siderophore uptake transmembrane transporter activityGO:0015344
Substrates: ferric-siderophore complex (extracellular)
Products: ferric-siderophore complex (periplasmic)

Processes

siderophore-iron import into cellGO:0033214

Locations

cell outer membraneGO:0009279

Binds extracellular ferric-siderophore complexes at the cell surface and, upon TonB engagement at its N-terminal plug-domain TonB box, undergoes conformational opening of the 22-stranded outer-membrane beta-barrel channel to import the complex into the periplasm.