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The TonB-dependent receptor Family [Function: Active transporters] Seed alignment | Full alignment | Pfam Wiki page | TC-DB page

This large family consists of receptors found in nearly all classes of Gram-negative bacteria and Cyanobacteria. These outer membrane proteins act as receptors for organic iron chelators (siderophores) and vitamins necessary for bacterial life. Members of this family are also termed TonB-dependent receptors because their action is mediated by the periplasmic domain of TonB protein. A complex of three membrane proteins (TonB, ExbB and ExbD) couples the chemiosmotic potential of the cytoplasmic membrane with siderophore uptake across the outer membrane. The crystallographic structures of several TonB-dependent Receptors (FhuA, FepA, FecA, BtuB, FusA) have recently been determined. These outer membrane receptors show a novel fold consisting of two domains. A 22-stranded antiparallel &ß-barrel traverses the outer membrane with the adjacent ß-strands being connected by large extracellular loops and periplasmic turns. At the N-terminal there is the Plug domain (of approximately 140 residues in length), located inside the &ß-barrel, which is composed primarily of a mixed 4-stranded ß sheets and a series of interspersed alpha helices. The Plug domain closes the channel pore and has been shown to interact with both the ligand and the periplasmic components. Ligand binding induces distinct local and allosteric transitions that establish the structural basis of signal transduction across the outer membrane.


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Literature references


Extracellular loops of BtuB facilitate transport of vitamin B12 through the outer membrane of E. coli
PLoS Comput Biol. 2020 Jul 1;16(7):e1008024. doi: 10.1371/journal.pcbi.1008024. eCollection 2020 Jul.
PMID: 32609716

Conformational rearrangements in the N-domain of Escherichia coli FepA during ferric enterobactin transport
J Biol Chem. 2020 Apr 10;295(15):4974-4984. doi: 10.1074/jbc.RA119.011850. Epub 2020 Feb 25.
PMID: 32098871

Identification of ireA, 0007, 0008, and 2235 as TonB-dependent receptors in the avian pathogenic Escherichia coli strain DE205B
Vet Res. 2020 Jan 23;51(1):5. doi: 10.1186/s13567-020-0734-z.
PMID: 31973724

A TonB-dependent transporter is required for secretion of protease PopC across the bacterial outer membrane
Nat Commun. 2019 Mar 25;10(1):1360. doi: 10.1038/s41467-019-09366-9.
PMID: 30911012

Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry
Science. 2018 Nov 16;362(6416):829-834. doi: 10.1126/science.aau0976.
PMID: 30442809

FusC, a member of the M16 protease family acquired by bacteria for iron piracy against plants
PLoS Biol. 2018 Aug 2;16(8):e2006026. doi: 10.1371/journal.pbio.2006026. eCollection 2018 Aug.
PMID: 30071011

Dissecting binding of a ß-barrel membrane protein by phage display
Mol Biosyst. 2017 Jul 25;13(8):1438-1447. doi: 10.1039/c7mb00163k.
PMID: 28627567

Going Outside the TonB Box: Identification of Novel FepA-TonB Interactions In Vivo
J Bacteriol. 2017 Apr 25;199(10):e00649-16. doi: 10.1128/JB.00649-16. Print 2017 May 15.
PMID: 28264993

Structural basis for nutrient acquisition by dominant members of the human gut microbiota
Nature. 2017 Jan 19;541(7637):407-411. doi: 10.1038/nature20828. Epub 2017 Jan 11.
PMID: 28077872

Confined Mobility of TonB and FepA in Escherichia coli Membranes
PLoS One. 2016 Dec 9;11(12):e0160862. doi: 10.1371/journal.pone.0160862. eCollection 2016.
PMID: 27935943

Structure of the bacterial plant-ferredoxin receptor FusA
Nat Commun. 2016 Oct 31;7:13308. doi: 10.1038/ncomms13308.
PMID: 27796364

TonB-dependent ligand trapping in the BtuB transporter
Biochim Biophys Acta. 2016 Dec;1858(12):3105-3112. doi: 10.1016/j.bbamem.2016.09.019. Epub 2016 Oct 6.
PMID: 27693114

The periplasmic domain of Escherichia coli outer membrane protein A can undergo a localized temperature dependent structural transition
Biochim Biophys Acta. 2014 Dec;1838(12):3014-24. doi: 10.1016/j.bbamem.2014.08.008. Epub 2014 Aug 15.
PMID: 25135663

Ligand-induced structural changes in the Escherichia coli ferric citrate transporter reveal modes for regulating protein-protein interactions
J Mol Biol. 2012 Nov 9;423(5):818-30. doi: 10.1016/j.jmb.2012.09.003. Epub 2012 Sep 11.
PMID: 22982293

TonB-dependent transporter FhuA in planar lipid bilayers: partial exit of its plug from the barrel
Biochemistry. 2012 Aug 28;51(34):6753-9. doi: 10.1021/bi300493u. Epub 2012 Aug 15.
PMID: 22846061

Structure, function and binding selectivity and stereoselectivity of siderophore-iron outer membrane transporters
Curr Top Membr. 2012;69:37-66. doi: 10.1016/B978-0-12-394390-3.00002-1.
PMID: 23046646

Heme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex
Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1045-50. doi: 10.1073/pnas.0809406106. Epub 2009 Jan 14.
PMID: 19144921

A beta strand lock exchange for signal transduction in TonB-dependent transducers on the basis of a common structural motif
Structure. 2007 Nov;15(11):1383-91. doi: 10.1016/j.str.2007.08.013.
PMID: 17997964

Structure of the complex of the colicin E2 R-domain and its BtuB receptor. The outer membrane colicin translocon
J Biol Chem. 2007 Aug 10;282(32):23163-70. doi: 10.1074/jbc.M703004200. Epub 2007 Jun 4.
PMID: 17548346

Structure of colicin I receptor bound to the R-domain of colicin Ia: implications for protein import
EMBO J. 2007 May 16;26(10):2594-604. doi: 10.1038/sj.emboj.7601693. Epub 2007 Apr 26.
PMID: 17464289

In meso structure of the cobalamin transporter, BtuB, at 1.95 A resolution
J Mol Biol. 2006 Dec 8;364(4):716-34. doi: 10.1016/j.jmb.2006.09.022. Epub 2006 Sep 12.
PMID: 17028020

Structure of TonB in complex with FhuA, E. coli outer membrane receptor
Science. 2006 Jun 2;312(5778):1399-402. doi: 10.1126/science.1128057.
PMID: 16741125

Outer membrane active transport: structure of the BtuB:TonB complex
Science. 2006 Jun 2;312(5778):1396-9. doi: 10.1126/science.1127694.
PMID: 16741124

Nuclear magnetic resonance solution structure of the periplasmic signalling domain of the TonB-dependent outer membrane transporter FecA from Escherichia coli
Mol Microbiol. 2005 Dec;58(5):1226-37. doi: 10.1111/j.1365-2958.2005.04889.x.
PMID: 16313612

Crystal structure at high resolution of ferric-pyochelin and its membrane receptor FptA from Pseudomonas aeruginosa
J Mol Biol. 2005 Sep 30;352(4):893-904. doi: 10.1016/j.jmb.2005.08.004.
PMID: 16139844

TonB-dependent outer membrane transport: going for Baroque?
Curr Opin Struct Biol. 2005 Aug;15(4):394-400. doi: 10.1016/j.sbi.2005.07.001.
PMID: 16039843

Binding of iron-free siderophore, a common feature of siderophore outer membrane transporters of Escherichia coli and Pseudomonas aeruginosa
J Biol Chem. 2005 May 27;280(21):20222-30. doi: 10.1074/jbc.M500776200. Epub 2005 Mar 22.
PMID: 15784620

The crystal structure of the pyoverdine outer membrane receptor FpvA from Pseudomonas aeruginosa at 3.6 angstroms resolution
J Mol Biol. 2005 Mar 18;347(1):121-34. doi: 10.1016/j.jmb.2005.01.021. Epub 2005 Jan 21.
PMID: 15733922

The solution structure of the C-terminal domain of TonB and interaction studies with TonB box peptides
J Mol Biol. 2005 Feb 4;345(5):1185-97. doi: 10.1016/j.jmb.2004.11.026. Epub 2004 Dec 15.
PMID: 15644214

The structure of BtuB with bound colicin E3 R-domain implies a translocon
Nat Struct Biol. 2003 Nov;10(11):948-54. doi: 10.1038/nsb997. Epub 2003 Oct 5.
PMID: 14528295

The Escherichia coli outer membrane cobalamin transporter BtuB: structural analysis of calcium and substrate binding, and identification of orthologous transporters by sequence/structure conservation
J Mol Biol. 2003 Oct 3;332(5):999-1014. doi: 10.1016/j.jmb.2003.07.005.
PMID: 14499604

Structural evidence for iron-free citrate and ferric citrate binding to the TonB-dependent outer membrane transporter FecA
J Mol Biol. 2003 Sep 12;332(2):353-68. doi: 10.1016/s0022-2836(03)00855-6.
PMID: 12948487

Mechanisms of iron acquisition by the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae
Front Biosci. 2003 Sep 1;8:d1186-218. doi: 10.2741/1133.
PMID: 12957813

Substrate-induced transmembrane signaling in the cobalamin transporter BtuB
Nat Struct Biol. 2003 May;10(5):394-401. doi: 10.1038/nsb914.
PMID: 12652322

TonB-dependent receptors-structural perspectives
Biochim Biophys Acta. 2002 Oct 11;1565(2):318-32. doi: 10.1016/s0005-2736(02)00578-3.
PMID: 12409204

Structural basis of gating by the outer membrane transporter FecA
Science. 2002 Mar 1;295(5560):1715-9. doi: 10.1126/science.1067313.
PMID: 11872840

Active transport of an antibiotic rifamycin derivative by the outer-membrane protein FhuA
Structure. 2001 Aug;9(8):707-16. doi: 10.1016/s0969-2126(01)00631-1.
PMID: 11587645

A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins
Structure. 2000 Jun 15;8(6):585-92. doi: 10.1016/s0969-2126(00)00143-x.
PMID: 10873859

Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA
Protein Sci. 2000 May;9(5):956-63. doi: 10.1110/ps.9.5.956.
PMID: 10850805

Crystal structure of the outer membrane active transporter FepA from Escherichia coli
Nat Struct Biol. 1999 Jan;6(1):56-63. doi: 10.1038/4931.
PMID: 9886293

Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide
Science. 1998 Dec 18;282(5397):2215-20. doi: 10.1126/science.282.5397.2215.
PMID: 9856937

Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes
Cell. 1998 Dec 11;95(6):771-8. doi: 10.1016/s0092-8674(00)81700-6.
PMID: 9865695

Proteins in this family with 3D-structure
View Entry
Description
Organism
Length
# strands
Ferrioxamine receptor FoxA
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
820
22
Ferric-anguibactin receptor FatA
Escherichia coli (strain K12)
729
22
Alginate_exp domain-containing protein
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
746
22
Putative outer membrane receptor for iron transport
Pseudomonas aeruginosa MH27
766
22
Major outer sheath protein
Escherichia coli (strain K12)
760
22
Putative copper transport outer membrane porin OprC
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
723
22
Probable outer membrane receptor for iron transport
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
753
22
TonB-dependent siderophore receptor
Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / CIP 70.34 / JCM6841 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81)
743
22
Nucleoside-specific channel-forming protein Tsx
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
720
20
Hemolysin activator-related protein
Neisseria meningitidis serogroup B (strain MC58)
915
24
Outer membrane protein A
Escherichia coli (strain K12)
746
22
Outer membrane protein assembly factor BamA
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
815
22
Uncharacterized protein
Neisseria meningitidis serogroup B (strain MC58)
758
22
HasR protein
Serratia marcescens
899
22
Outer membrane protein assembly factor BamA
Yersinia pestis
673
14
Fe-regulated protein B
Neisseria meningitidis
720
22
Ferric alcaligin siderophore receptor
Bordetella pertussis
734
22
Enantio-pyochelin receptor
Pseudomonas fluorescens
743
22
Ferric-anguibactin receptor FatA
Escherichia coli (strain K12)
663
22
Ferrichrome outer membrane transporter/phage receptor
Escherichia coli (strain K12)
747
22
Iron-regulated outer membrane protein
Neisseria meningitidis
672
20
Vitamin B12 transporter BtuB
Escherichia coli (strain K12)
614
22
Outer membrane heme receptor ShuA
Shigella dysenteriae
660
22
Ferric-anguibactin receptor FatA
Escherichia coli (strain K12)
774
22
TonB-dependent siderophore receptor
Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / CIP 70.34 / JCM6841 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81)
754
22
Ferric enterobactin receptor PirA
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
742
22
Plug domain-containing protein
Pectobacterium atrosepticum (strain SCRI 1043 / ATCC BAA-672) (Erwiniacarotovora subsp. atroseptica)
860
22


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