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). The precursor contains an N-terminal signal peptide (residues 1-17), a periplasm-facing N-terminal plug (cork) domain (Pfam PF07715, residues 60-159) with a conserved TonB box motif, and a 22-stranded outer-membrane beta-barrel domain (Pfam PF00593, residues 265-709). Upon binding extracellular ferric-siderophore or photoreactive lipopeptide complexes such as variobactin at the cell surface, BfrD1 interacts via its N-terminal TonB box with periplasmic TonB to couple inner-membrane proton-motive force to plug-domain unfolding and active import of the iron chelate into the periplasmic space.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0009279 cell outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Core subcellular localization supported by the N-terminal signal peptide (residues 1-17) and C-terminal 22-stranded outer-membrane TonB-dependent receptor beta-barrel domain (Pfam PF00593, residues 265-709). Reason: BfrD1 possesses a cleavable Sec signal peptide (residues 1-17) followed by a canonical outer-membrane TonB-dependent receptor plug domain (residues 60-159) and transmembrane beta-barrel domain (residues 265-709), placing the mature receptor in the Gram-negative cell outer membrane. Supporting Evidence: UniProtKB:A0A0H2M677 SUBCELLULAR LOCATION: Cell outer membrane {ECO:0000256|ARBA:ARBA00004571, ECO:0000256|PROSITE-ProRule:PRU01360}; Multi-pass membrane protein PMID:20420522 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. |
| GO:0015343 siderophore-iron transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct but general parent term; refine to the more specific child term GO:0015344 (siderophore uptake transmembrane transporter activity) already carried by this protein. Reason: GO:0015344 (siderophore uptake transmembrane transporter activity) is a direct is_a child of GO:0015343 that is already accepted on this protein and specifies the inward import direction of TonB-dependent outer-membrane ferric-siderophore receptors. Proposed replacements: siderophore uptake transmembrane transporter activity Supporting Evidence: UniProtKB:A0A0H2M677 DR InterPro; IPR010105; TonB_sidphr_rcpt. |
| GO:0015344 siderophore uptake transmembrane transporter activity | IEA GO_REF:0000118 | ACCEPT | Summary: Core molecular function of BfrD1 as a TonB-dependent outer-membrane ferric-siderophore uptake transporter. Reason: BfrD1 belongs to the TonB-dependent siderophore receptor family (InterPro:IPR010105, TIGR01783, PANTHER:PTHR32552) and is encoded adjacent to tonB (VPARA_25820), mediating active uptake of ferric-siderophore complexes across the outer membrane. Supporting Evidence: UniProtKB:A0A0H2M677 DR InterPro; IPR010105; TonB_sidphr_rcpt. PMID:20420522 The first crystal structures of two Escherichia coli TonB-dependent transporters, ferrichrome transporter (FhuA) (34, 54) and ferric enterobactin transporter (FepA) (10), showed that TBDTs use a 22-stranded Ξ²-barrel to span the outer membrane with an unanticipated βplugβ domain folded into the barrel interior. |
| GO:0015891 siderophore transport | IEA GO_REF:0000002 | MODIFY | Summary: Correct but general biological process term; refine to GO:0033214 (siderophore-iron import into cell) already carried by this protein. Reason: GO:0033214 (siderophore-iron import into cell) is already accepted on this protein and more specifically captures both the ferric-siderophore cargo and cellular import direction mediated by outer-membrane TonB-dependent receptors. Proposed replacements: siderophore-iron import into cell Supporting Evidence: UniProtKB:A0A0H2M677 DR InterPro; IPR010105; TonB_sidphr_rcpt. |
| GO:0033214 siderophore-iron import into cell | IEA GO_REF:0000120 | ACCEPT | Summary: Core biological process representing TonB-energized import of ferric-siderophore complexes across the bacterial outer membrane. Reason: As an outer-membrane TonB-dependent ferric-siderophore receptor paired genomically with tonB (VPARA_25820), BfrD1 mediates the primary entry step of ferric-siderophore import into the cell. Supporting Evidence: UniProtKB:A0A0H2M677 DR InterPro; IPR010105; TonB_sidphr_rcpt. PMID:20420522 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. PMID:26412281 The crude extract of V. paradoxus P4B was shown to contain a series of candidate hits (Fig. 2b) whose isolation yielded the novel natural products variobactin A and B |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | REMOVE | Summary: Automated InterPro2GO over-annotation from IPR010105; BfrD1 is a canonical 739-aa transport receptor lacking an N-terminal FecR-coupled anti-sigma transmembrane signaling extension. Reason: In the TonB-dependent receptor superfamily, only the specialized TonB-dependent transducer subclass (such as E. coli FecA or P. aeruginosa FpvA) possesses an ~80-100 residue N-terminal periplasmic signaling domain (Pfam PF07660) upstream of the plug domain that engages an inner-membrane anti-sigma factor to transduce a transcriptional signal. BfrD1 is 739 residues in total with its signal peptide at residues 1-17 and its plug domain starting directly at residue 60 (residues 60-159), lacking any N-terminal signaling extension. Its biological role is transmembrane ferric-siderophore import rather than signal transduction. Supporting Evidence: UniProtKB:A0A0H2M677 FT SIGNAL 1..17 PMID:20420522 The first crystal structures of two Escherichia coli TonB-dependent transporters, ferrichrome transporter (FhuA) (34, 54) and ferric enterobactin transporter (FepA) (10), showed that TBDTs use a 22-stranded Ξ²-barrel to span the outer membrane with an unanticipated βplugβ domain folded into the barrel interior. |
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Download this section (compressed HTML)Q: Does BfrD1 (VPARA_25830) serve as the primary outer-membrane receptor for endogenous variobactin/vacidobactin ferric-siderophore complexes in Variovorax paradoxus, or does it specialize in xenosiderophore (ferrichrome/enterobactin) piracy in the rhizosphere?
Suggested experts: Cornelis P, Noinaj N, Leadbetter JR
Experiment: Construct a ΞbfrD1 deletion mutant in Variovorax paradoxus TBEA6 and assay iron-limited growth rescue with purified Fe(III)-variobactin, ferrichrome, and enterobactin chelates, alongside isothermal titration calorimetry of purified detergent-solubilized BfrD1 with ferric-variobactin.
Hypothesis: BfrD1 binds ferric-siderophore chelates with nanomolar affinity and mediates TonB-dependent iron acquisition under rhizosphere iron limitation.
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