1.B.14 The Outer Membrane Receptor (OMR) Family

The OMR family includes a large number of sequenced Gram-negative bacterial outer membrane proteins which form transmembrane pores and transport relatively large molecules from the external milieu to the periplasm in an energized process. Although represented in cyanobacteria, no OMR member has been identified in a Gram-positive bacterium, an archaeon or a eukaryote. Energization of transport across the outer membrane requires a heterotrimeric complex of proteins, the TonB-ExbB-ExbD complex, or in some cases, the TolA-TolQ-TolR complex (TC #10.6). Energization requires the proton motive force (pmf) across the cytoplasmic membrane. In the absence of a pmf or one of the three energy coupling proteins of the complex, the receptor binds its substrate, but transport does not occur. Substrates transported by OMR family members include iron-siderophore complexes, vitamin B12, Cu2+, colicins (group B colicins are transported via TonB-dependent receptors while group A colicins are transported via TolA-dependent receptors), and the DNA of various phage. OMR proteins are also essential for the utilization of iron from eukaryotic proteins such as transferrin, hemoglobin and hemin. The vitamin B12, and iron-siderophore receptors feed into ABC-type permeases (TC #3.A.1.13 and 3.A.1.14) for transport across the cytoplasmic membrane. Alteration (e.g., small internal deletions) of some OMR members can convert them into diffusion channels. Normally, they probably form ligand-specific and energy-gated pores through the outer membranes of Gram-negative bacteria. However, the fact that minor genetic changes result in the generation of diffusion channels suggests that these proteins form large porin-like β-barrel structures.

The three-dimensional structure of one OMR family member, FhuA (TC #1.B.14.1.4), has been elucidated in two conformations, one with and one without bound ferrichrome-iron, both at about 2.6 = resolution (see Ferguson and Deisenhofer (2004) for a review summarizing function/structure relationships). FhuA is a β-barrel composed of 22 antiparallel β-strands. In contrast to the trimeric arrangement seen in most porins, FhuA is monomeric. Located within the β-barrel is a domain called the 'cork' which consists of a four-stranded β-sheet and four short α-helices. The cork closes the channel, but without the cork, there is no activity (Braun et al., 2003). The barrel and cork can be synthesized as separate polypeptide chains, and activity is still observed. The β-barrel is made first, and the cork is inserted later, extracytoplasmically (Braun et al., 2003). A single lipopolysaccharide is tightly associated with the transmembrane region of FhuA. Upon binding of ferrichrome-iron in an aromatic pocket near the cell surface, conformational changes are transduced to the periplasmic face of FhuA, signaling ligand-loading. Based on these findings, a structural model for TonB-dependent, FhuA-mediated siderophore-iron transport across the outer membrane of E. coli has been proposed. Substrate binding induces long-range structural changes that involve gating (Braun and Braun, 2002). Moreover, a ternary complex of FhuA, TonB and FhuD (the periplasmic ABC-type binding receptor) has been demonstrated (Carter et al., 2006). FhuD accepts ferrichrome from FhuA and passes it on to its ABC transporter. Some of these transporters are involved in siderophore-mediated signaling cascades that sense signals at the cell surface and control transcription of genes encoding proteins for siderophore transport and biosynthesis (Braun and Braun, 2002).

Three structures of the Serratia marcescens receptor, HasR (1.B.14.5.1) in complex with its hemophore HasA, have been solved (Krieg et al., 2009). The transfer of heme over a distance of 9 A from its high-affinity site in HasA into a site of lower affinity in HasR is coupled with the exergonic complex formation of the 2 proteins. Upon docking to the receptor, 1 of the 2 axial heme coordinations of the hemophore is initially broken, but the position and orientation of the heme is preserved. Subsequently, steric displacement of heme by a receptor residue ruptures the other axial coordination, leading to heme transfer into the receptor (Krieg et al., 2009).

OprC of Pseudomonas aeruginosa and NosA of P. stutzeri are two large outer membrane receptors that exhibit copper-binding (Kd = 2.6 µM), channel-forming, and Cu2+ transporting characteristics. Liposome swelling assays with the purified protein and planar bilayer ion conductance measurements suggest that OprC forms small channels after the precursors form (723 aas) is processed to the mature form (668 aas). NosA of P. stutzeri is 65% identical to OprC, and it conveys Cu2+ to intracellular acceptors. OprC synthesis is repressed by exogenous Cu2+ and derepressed by anaerobiosis in the presence of nitrate, results consistent with the conclusion that both it and NosA are involved in copper utilization.

Both one- and two-component TonB-dependent transport systems are known. Most OMRs are single-component systems and are analogous to the well-characterized siderophore receptors (TC #1.B.14.1.1-1.B.14.1.4 below). Two component systems consist of a TonB-dependent receptor homologous to those of the one component systems as well as an accessory lipoprotein. The HpuAB pair (TC #9.14.2.4 below) is one example of such a system, while the TbpAB (TC #1.B.14.2.1) and the LbpAB (TC #1.B.14.2.5) systems are two other examples. The LbpB and TbpB lipoproteins are homologous, but the smaller HpuA lipoprotein is not demonstrably homologous to either LbpB and TbpB.

The HasR receptors of Serratia marcescens and Pseudomonas aeruginosa use an extracellular processed haemophore, HasA, that captures free or haemoglobin-bound haem and shuttles it to HasR in preparation for transport across the outer membrane by a TonB-dependent mechanism. HasA is a monomeric protein that binds haem with very high affinity (Kd lower than 10-8 M) and binds HasR both in the heme-free and heme-loaded forms with a Kd of about 10-10. It is exported via an ABC-type export system. The iron-regulated iron-siderophore yersiniabactin receptors are also the pesticin receptors of Yersinia species which provide the route entry of the bacteriocin, pesticin.

Wolff et al. (2007) reported the 3-D NMR structure of apoHasA and the backbone dynamics of both loaded and unloaded hemophore. While the overall structure of HasA is very similar in the apo and holo forms, the hemophore presents a transition from an open to a closed form upon ligand binding, through a large movement, of up to 30 A, of loop L1 bearing H32. Comparison of loaded and unloaded HasA dynamics on different time scales reveals striking flexibility changes in the binding pocket. These features provide the dual function of heme binding and release to the HasR receptor (Wolff et al., 2007).

The structure of the BtuB outer membrane receptor (OMR; 1.B.14.3.1) and the FhuA OMR (1.B.14.1.4) complexed with the C-terminal domain of TonB (2.C.1.1.1), the energy transmitter to the OMR from the ExbBD energizer, shows TonB binding to the TonB box in the OMRs. TonB binding causes the TonB box to form a β-strand, forming a β-sheet with TonB's own β-strand. This is consistent with a mechanical 'pulling' mechanism of transport (Shultis et al., 2006). The conserved TonB arginine 166 is oriented to form multiple contacts with the FhuA 'cork', the globublar domain enclosed by the β-barrel (Pawelek et al., 2006).


Transport results from energy-driven movement of the TonB protein, which either pulls the plug out of the barrel or causes it to rearrange within the barrel. Udho et al. (2009) discovered that if the cis solution contains 4 M urea, then, with the periplasmic side of the channel facing that solution, macroscopic conductances and single channel events can be observed with FhuA, Cir, and BtuB. Channels generated by 4 M urea exposure were not a consequence of general protein denaturation as their ligand-binding properties were preserved. Thus, with FhuA, addition of ferrichrome (its siderophore) to the trans, extracellular-facing side reversibly inhibited 4 M urea-induced channel opening while blocking the channel (Shultis et al., 2006). With Cir, addition of colicin Ia (the microbial toxin that targets Cir) to the trans, extracellular-facing side, prevented 4 M urea-induced channel opening. Maybe 4 M urea reversibly unfolds the plugs, thereby opening an ion-conducting pathway through these channels. This might mimic the in vivo action of TonB on these plugs (Udho et al., 2009).

TonB-dependent transporters bind and transport ferric chelates, vitamin B12, nickel complexes, and carbohydrates. The transport process requires energy in the form of the pmf and the TonB-ExbB-ExbD complex to transduce this energy to the outer membrane. The siderophore substrates range in complexity from simple small molecules such as citrate to large proteins such as serum transferrin and hemoglobin. Expression can be regulated by metal-dependent regulators, σ/anti-σ factors, small RNAs, and a riboswitch (Noinaj et al., 2010). Noinaj et al. (2010) summarized the regulation, structure and function of these systems.

The generalized transport reaction for proteins of the OMR family is:

Substrate (out) Substrate (periplasm)



This family belongs to the Outer Membrane Pore-forming Protein (OMPP) Superfamily I.

 

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Shultis, D.D., M.D. Purdy, C.N. Banchs, and M.C. Wiener. (2006). Outer membrane active transport: structure of the BtuB:TonB complex. Science 312: 1396-1399.

Sikora, A., B. Joseph, M. Matson, J.R. Staley, and D.S. Cafiso. (2016). Allosteric Signaling Is Bidirectional in an Outer-Membrane Transport Protein. Biophys. J. 111: 1908-1918.

Smajs, D. and G.M. Weinstock. (2001). The iron- and temperature-regulated cjrBC genes of Shigella and enteroinvasive Escherichia coli strains code for colicin Js uptake. J. Bacteriol. 183: 3958-3966.

Udho, E., K.S. Jakes, S.K. Buchanan, K.J. James, X. Jiang, P.E. Klebba, and A. Finkelstein. (2009). Reconstitution of bacterial outer membrane TonB-dependent transporters in planar lipid bilayer membranes. Proc. Natl. Acad. Sci. USA 106: 21990-21995.

van Vliet, A.H., J. Stoof, R. Vlasblom, S.A. Wainwright, N.J. Hughes, D.J. Kelly, S. Bereswill, J.J. Bijlsma, T. Hoogenboezem, C.M. Vandenbroucke-Grauls, M. Kist, E.J. Kuipers, and J.G. Kusters. (2002). The role of the Ferric Uptake Regulator (Fur) in regulation of Helicobacter pylori iron uptake. Helicobacter 7: 237-244.

Vanderpool, C.K. and S.K. Armstrong. (2004). Integration of environmental signals controls expression of Bordetella heme utilization genes. J. Bacteriol. 186: 938-948.

Vianney, A., T.M. Lewin, W.F. Beyer, Jr., J.C. Lazzaroni, R. Portalier, and R.E. Webster. (1994). Membrane topology and mutational analysis of the TolQ protein of Escherichia coli required for the uptake of macromolecules and cell envelope integrity. J. Bacteriol. 176: 822-829.

Wei, X., L.A. Sayavedra-Soto, and D.J. Arp. (2007). Characterization of the ferrioxamine uptake system of Nitrosomonas europaea. Microbiology. 153: 3963-3972.

Wexler, H.M., E.K. Read, and T.J. Tomzynski. (2002). Characterization of omp200, a porin gene complex from Bacteroides fragilis: omp121 and omp71, gene sequence, deduced amino acid sequences and predictions of porin structure. Gene 283: 95-105.

Wojtowicz, H., A. Prochnicka-Chalufour, G. Cardoso de Amorim, O. Roudenko, C. Simenel, I. Malki, G. Pehau-Arnaudet, F. Gubellini, A. Koutsioubas, J. Perez, P. Delepelaire, M. Delepierre, R. Fronzes, and N. Izadi-Pruneyre. (2016). Structural basis of the signaling through a bacterial membrane receptor HasR deciphered by an integrative approach. Biochem. J. [Epub: Ahead of Print]

Wolfe AJ., Mohammad MM., Thakur AK. and Movileanu L. (2016). Global redesign of a native beta-barrel scaffold. Biochim Biophys Acta. 1858(1):19-29.

Wolff, N., N. Izadi-Pruneyre, J. Couprie, M. Habeck, J. Linge, W. Rieping, C. Wandersman, M. Nilges, M. Delepierre, and A. Lecroisey. (2008). Comparative analysis of structural and dynamic properties of the loaded and unloaded hemophore HasA: functional implications. J Mol Biol 376: 517-25.

Xiong, K., Z. Chen, C. Zhu, J. Li, X. Hu, X. Rao, and Y. Cong. (2015). Safety and immunogenicity of an attenuated Salmonella enterica serovar Paratyphi A vaccine candidate. Int. J. Med. Microbiol. 305: 563-571.

Xiong, K., Z. Chen, G. Xiang, J. Wang, X. Rao, F. Hu, and Y. Cong. (2012). Deletion of yncD gene in Salmonella enterica ssp. enterica serovar Typhi leads to attenuation in mouse model. FEMS Microbiol. Lett. 328: 70-77.

Yang, J.N., C. Wang, C. Guo, X.X. Peng, and H. Li. (2011). Outer membrane proteome and its regulation networks in response to glucose concentration changes in Escherichia coli. Mol Biosyst 7: 3087-3093.

Ye, L., S. Matthijs, J. Bodilis, F. Hildebrand, J. Raes, and P. Cornelis. (2014). Analysis of the draft genome of Pseudomonas fluorescens ATCC17400 indicates a capacity to take up iron from a wide range of sources, including different exogenous pyoverdines. Biometals 27: 633-644.

Yoneyama, H. and T. Nakae. (1996). Protein C (OprC) of the outer membrane of Pseudomonas aeruginosa is a copper-regulated channel protein. Microbiology 142(Pt8): 2137-2144.

Zhu, Y., K.J. Kwiatkowski, T. Yang, S.S. Kharade, C.M. Bahr, N.M. Koropatkin, W. Liu, and M.J. McBride. (2015). Outer membrane proteins related to SusC and SusD are not required for Cytophaga hutchinsonii cellulose utilization. Appl. Microbiol. Biotechnol. 99: 6339-6350.

Examples:

TC#NameOrganismal TypeExample
1.B.14.1.1FhuE ferric-coprogen Gram-negative bacteria FhuE of E. coli
 
1.B.14.1.10The outer membrane ferrioxamine/desferrioxamine receptor, FoxA(1) (most like TC# 1.B.14.1.4 and 9) (Wei et al., 2007)BacteriaFoxA(1) of Nitrosomonas europaea (Q82VI7)
 
1.B.14.1.11The outer membrane ferric-anguibactin receptor/transporter, FatA (Lopez and Crosa, 2007)BacteriaFatA of Vibrio anguillarum (P11461)
 
1.B.14.1.12FecA ferric-citrate receptor (PA3901) (Marshall et al., 2009) (62% identical to the E. coli FecA).

Gram-negative bacteria

FecA of Pseudomonas aeruginosa (Q9HXB2)

 
1.B.14.1.13CfrA ferric receptor (Carswell et al., 2008).

Gram-negative bacteria

CfrA of Campylobacter jejuni (A3ZKG8)

 
1.B.14.1.14Ferric-pseudobactin 358 receptorBacteria

PupA of Pseudomonas putida

 
1.B.14.1.15Ferrichrome receptor FcuABacteriaFcuA of Yersinia enterocolitica
 
1.B.14.1.16Probable TonB-dependent receptor BfrD (Virulence-associated outer membrane protein Vir-90)BacteriaBfrD of Bordetella pertussis
 
1.B.14.1.17

Ferrioxamine receptor, FoxA.  Transports a variety of Ferrioxamine B analogues (Kornreich-Leshem et al. 2005).

Bacteria

FoxA of Yersinia enterocolitica

 
1.B.14.1.18

TonB-dependent receptor (Bhat et al. 2011).

Proteobacteria

TonB-dependent receptor of Myxococcus xanthus

 
1.B.14.1.19

TonB-dependent receptor

Proteobacteria

TonB-dependent receptor of Myxococcus xanthus

 
1.B.14.1.2

FhuA ferrichrome (also albomycin and rifamycin; Colicin M; Microcin J25; Phage T5) receptor (transports phage T1, T5 and φ80 DNA across the outer membrane, dependent on DcrA (SdaC; TC #2.A.42.2.1) and DcrB) (Forms a complex with and acts with TonB and FhuD (the periplasmic binding receptor (3.A.1.14.3) to deliver siderophore to FhuD (Carter et al., 2006; Braun et al., 2009)).  Deletion of the 160-residue cork domain and five large extracellular loops converted this non-conductive, monomeric, 22-stranded beta-barrel protein into a large-conductance protein pore (Wolfe et al. 2015).

Gram-negative bacteria

FhuA of E. coli

 
1.B.14.1.20

The iron-citrate receptor/transporter, FecA.  TonB mediates both signaling and transport by unfolding portions of the transporter (Mokdad et al. 2012).

Bacteria

FecA of E. coli

 
1.B.14.1.21

Ferrioxamine receptor

γ-Proteobacteria

Ferrioxamine receptor of Pseudovibrio sp. JE062

 
1.B.14.1.22

FepA ferri-enterobactin (also Colicins B and D) receptor for the 37 aas disulfide-containing K+ channel toxin, BgK (Braud et al., 2004). Functions by a "ball and chain" mechanism; The transport process involves expulsion of the N-terminal globular domain from the C-terminal beta-barrel (Ma et al. 2007).

Gram-negative bacteria

FepA of E. coli

 
1.B.14.1.23

OMR of 938 aas

Proteobacteria

OMR of Myxococcus xanthus

 
1.B.14.1.24

Putative TonB-dependent siderophore receptor, Sde_3611

Proteobacteria

Sde3611 of Saccharophagus degradans

 
1.B.14.1.25

Nickel uptake receptor/channel of 724 aas (Benoit et al. 2013).

Proteobacteria

HH0418 of Helicobacter hepaticus

 
1.B.14.1.26

Iron siderophore (ferripyoverdine) receptor, FpvA of 808 aas (Ye et al. 2014).

Proteobacteria

FpvA of Pseudomonas aeruginosa

 
1.B.14.1.27

Iron(III) dicitrate transport protein, FecA1: iron dicitrate uptake receptor of 767 aas.  Regulated by the ferric uptake regulator transcription factor, Fur (van Vliet et al. 2002) in response to iron availability (Danielli et al. 2009). Involved in iron deficiency anemia in children (Kato et al. 2017).

FecA1 of Helicobacter pylori

 
1.B.14.1.28

FecA3 of 843 aas.  Probable receptor for nickel.  Shows 50% identiy with TC# 1.B.14.1.27. Repressed by nickel in the medium, mediated by NikR (Danielli et al. 2009). NikR seems to interact in an asymmetric mode with the fecA3 target to repress its transcription (Romagnoli et al. 2011).

FecA3 of Helicobacter pylori

 
1.B.14.1.29

Iron-deficiency-induced (2x) iron siderophore uptake outer membrane receptor, FhuA, of 828 aas and 1 N-terminal TMS (Qiu et al. 2018). 

FhuA of Synechocystis sp. (strain PCC 6803 / Kazusa)

 
1.B.14.1.3

Ferric enterobactin (also ferricorynebactin) receptor, IroN

Gram-negative bacteria

IroN of Salmonella typhimurium

 
1.B.14.1.30

Outer membrand iron siderophore uptake receptor of 853 aas and 1 N-terminal TMS, Slr1490.

Slr1490 of Synechocystis sp. (strain PCC 6803 / Kazusa)

 
1.B.14.1.31

Outer membrane porin, PiuA, of 753 aas.  A deficiency of this iron transporter, PiuA in P. aeruginosa, caused 16-fold increases in cefiderocol resistance, suggesting that it contribute to the permeation of cefiderocol into the cell (Ito et al. 2018).

PiuA of Pseudomonas aeruginosa

 
1.B.14.1.4

CirA Fe3+-catecholate receptor. Serves as the receptor for the TonB- and proton-dependent uptake of the E. coli bacteriocin, Microcin L (MccL) (Morin et al., 2011). CirA is also the translocator for colicin Ia (Jakes and Finkelstein, 2010). Plays roles in cefiderocol and ceftazidime resistance (Ito et al. 2018).

Gram-negative bacteria

CirA of E. coli

 
1.B.14.1.5PfeA ferric enterobactin receptor Gram-negative bacteria PfeA of Pseudomonas aeruginosa
 
1.B.14.1.6

Ferripyoverdine/pyocin S3 receptor, FpvA (Adams et al., 2006; Nader et al., 2007; Schalk et al., 2009Nader et al., 2011)

Gram-negative bacteria

FpvA of Pseudomonas aeruginosa

 
1.B.14.1.7Iron malleobactin receptor, FmtA (Alice et al., 2006)Gram-negative bacteriaFmtA of Burkholderia pseudomallei (EBA51007)
 
1.B.14.1.8

The Ferripyochelin receptor, FptA (Michel et al., 2007). In addition to Fe3+, FptA takes up Co2+, Ga3+, and Ni2+ at low rates (Braud et al., 2009). The high resolution 3-d structure of FptA (2.0 Å) bound to iron-pyochelin has been solved (Cobessi et al. 2005). The pyochelin molecule provides atetra-dentate coordination of iron. The structure is typical of the TonB-dependent receptor/transporter superfamily.

Gram-negative bacteria

FptA of Pseudomonas aeruginosa (P42512)

 
1.B.14.1.9

Ferric-catecholate siderophore (dihydroxybenzoylserine, dihydroxybenzoate) uptake receptor, Fiu or YbiL (Hantke, 1990; Curtis et al., 1988). Plays roles in cefiderocol and ceftazidime resistance (Ito et al. 2018).

Gram-negative bacteria

Fiu of E. coli (P75780)

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.10.1Heme/hemoglobin receptor, HmuR (also binds the Cu2+, Zn2+ and Fe2+ derivatives of protoporphyrin IX). Functions with the O.M. heme binding lipoprotein, HmuY (AAQ66587; Olczak et al., 2007).Gram-negative bacteriaHmuR of Porphyromonas gingivalis
 
1.B.14.10.2

TonB-dependent receptor

Proteobacteria

TonB receptor of Myxococcus xanthus

 
1.B.14.10.3

TonB-dependent receptor

Proteobacteria

TonB recpetor of Myxocuccus xanthus

 
1.B.14.10.4

Putative TonB-dependent receptor

Cyanobacteria

OMR of Gloeobacter violaceus

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.11.1

The Nickel (Ni2+) receptor (FrpB4; Hp1512) of 877 aas. Energized by the TonB/ExbBD complex (Schauer et al., 2007). Capable of binding both haem and haemoglobin but shows greater affinity for haem. The mRNA levels of frpB1 were repressed by iron and lightly modulated by haem or haemoglobin. Overexpression of the frpB1 gene supported cellular growth when haem or haemoglobin were supplied as the only iron source (Carrizo-Chávez et al. 2012).

Gram-negative bacteria

FrpB4 of Helicobacter pylori (Q9ZJA8)

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.12.1The TonB-dependent maltooligosaccharide OM receptor/porin, MalA (Lohmiller et al., 2008).BacteriaMalA of Caulobacter crescentus (Q9A608)
 
1.B.14.12.2The N-acetyl glucosamine/chitin oligosaccharide OM receptor porin, NagA (Eisenbeis et al., 2008).BacteriaNagA of Caulobacter crescentus (Q9AAZ6)
 
1.B.14.12.3

TonB-dependent receptor

Proteobacteria

TonB-dependent receptor of Myxococcus xanthus

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.13.1

TonB-dependent receptor of 763 aas

Proteobacteria

Receptor of Xanthomonas campestris

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.14.1

The thiamine receptor (BT2390) (energized by TonB/ExbBD) (Rodionov et al. 2002).

Bacteroidetes

BT2390 of Bacteroides thetaiotaomicron (Q8A552)

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.15.1

Putative porin of the DUF4289 family; 655 aas and 32 putative transmembrane beta strands.

Bacteroidetes

PP of Psychroflexus torquis

 
1.B.14.15.2

Putative porin of 776 aas

Bacteroidetes

PP of Provotella ruminicola

 
1.B.14.15.3

Putative porin of 631 aas

Bacteroidetes

PP of Amoebophilus asiaticus

 
1.B.14.15.4

Putative DUF4289 family porin of 687 aas

Bacteroidetes

PP of Niastella koreensis

 
1.B.14.15.5

Putative porin of 627 aas

Bacteroidetes

PP of Melioribacter roseus

 
1.B.14.15.6

Putative porin of 650 aas

Ignavibacteriae

PP of Ignavibacterium album

 
1.B.14.15.7

Putative porin of 621 aas

Bacteroidetes

PP of Cryptocercus punctulatus

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.16.1

DUF940 homologue of 720 aas, one signal sequence and 30 putative β-strands.  Homologous to proteins designated YmcA, WbfB and YjbH.

Chlamydiae

DUF940 homologue of Protochlamydia amoebophila

 
1.B.14.16.10

Putative LPS exporter receptor, OtuG.  It's gene is in a cluster with several LPS biosynthetic enzymes.

Proteobacteria

OtuG of Vibrio parahaemolyticus

 
1.B.14.16.11

OMR of 698 aas and 1 N-terminal TMS, GlfD or YmcA.  Probably involved in capsular polysaccharide export (Peleg et al. 2005).

GlfD of E. coli

 
1.B.14.16.2

DUF940 homologue of 953 aas, one N-terminal signal sequence and 30 putative beta strands.

Proteobacteria

DUF940 homologue of Chromobacterium violaceum

 
1.B.14.16.3

DUF940 homologue of 689 aas, one N-terminal signal sequence and 28 putative TM β-strands.

Proteobacteria

DUF940 homologue of Psychromonas ingrahamii

 
1.B.14.16.4

DUF940 homologue of 940 aas, one N-terminal signal sequence and 32 putative TM β-strands.

Proteobacteria

DUF940 homologue of E. coli

 
1.B.14.16.5

DUF940 homologue of 716 aas with one N-terminal signal sequence and 27 putative beta strands.

Chlamydiae

DUF940 homologue of Parachlamydia acanthamoebae

 
1.B.14.16.6

DUF940 homologue of 718 aas, an N-terminal signal sequence and 33 putative beta strands.

Proteobacteria

DUF940 homologue of Photobacterium angustum

 
1.B.14.16.7

Putative polysaccharide exporter of 690 aas and 34 predicted TMSs, WbfB.  Encoded in a gene cluster with polysaccharide biosynthetic enzymes and a putative periplasmic polysaccharide export protein.

Proteobacteria

Putative OMR concerned with polysaccharide export of Syntrophus aciditrophicus

 
1.B.14.16.8

Putative polysaccharide/glycolipid/glycoprotein export receptor of 736 aas and 30 predicted β-strands, WbfB.  The gene encoding this protein is in a cluster with UDP-N-acetyl D-quinovosamine -4 epimerase.

Proteobacteria

Putative exporter of Vibrio anguillarum

 
1.B.14.16.9

Putative lipopolysaccharide export receptor, WbfB.  It is encoded in a gene cluster with LPS biosynthetic genes.

Proteobacteria

WbfB of Vibrio parahaemolyticus

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.17.1

Uncharacterized protein of 922 aas

Bacteroidetes

UP of Dyadobacter fermentans

 
1.B.14.17.2

Putative Planctomycetes OMR of 799 aas

Planctomycetes

Putative OMR of Planctomyces brasiliensis

 
1.B.14.17.3

Putative Planctomycetes OMR of 1101 aas

Planctomycetes

Putative OMR of Isosphaera pallida

 
1.B.14.17.4

Uncharacterized protein of 1055 aas

Lentisphaerae

UP of Lentisphaera araneosa

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.18.1

Putative Verucomicrobial OMP of 676 aas 

Verucomicrobia

Putative OMR of Optutus terrae

 
1.B.14.18.2

Uncharacterized OM channel superfamily member of 791 aas

Verrucomicrobia

UP of Pedosphaera parvula

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.2.1

HmbR Hemoglobin receptor

Gram-negative bacteria HmbR of Neisseria meningitidis
 
1.B.14.2.10Heme transporter BhuA (Brucella heme uptake protein A)Bacteria

BhuA of Brucella abortus

 
1.B.14.2.11Heme/hemopexin utilization protein CBacteriaHxuC of Haemophilus influenzae
 
1.B.14.2.12

The transferrin receptor/lipoprotein complex, TbpAB (TbpA receptor, 912aas; TbpB lipoprotein, 625aas)

γ-Proteobacteria

TbpAB of Haemophilus influenzae
TbpA (P44970)
TbpB (P44971)

 
1.B.14.2.13

Hemoglobin receptor, HgbA.  Residues for hemoglobin binding and utilization differ (Fusco et al. 2013).

Proteobacteria

HgbA of Haemophilus ducreyi

 
1.B.14.2.14

Heme/hemoglobin receptor of 660 aas and 22 C-terminal β-strands with an N-terminal "plug" domain, ShuA.  The 3-d structure is known to 2.6 Å resolution, revealing the histidyl residues in the barrel and plug that can interact with heme (Cobessi et al. 2010).

Proteobacteria

ShuA of Shigella dysenteriae

 
1.B.14.2.15
Uncharacterized outer membrane receptor, probably for iron transport.

Proteobacteria

OMR of Xanthomonas oryzae
 
1.B.14.2.2HemR Heme (Hemin) receptor Gram-negative bacteria HemR of Yersinia enterocolitica
 
1.B.14.2.3HpuAB hemoglobin-haptoglobin receptor; porphyrin transporter (HpuA=lipoprotein; HpuB=OMR porin) Gram-negative bacteria HpuAB of Neisseria meningitidis
 
1.B.14.2.4

Lactoferrin receptor (A=OMR porin; B=lipoprotein), LbpAB or IroAB. This two-component system extracts iron from the host glycoproteins lactoferrin and transferrin. Homologous iron-transport systems consist of a membrane-bound transporter and an accessory lipoprotein. The crystal structure of the N-terminal domain (N-lobe) of the accessory lipoprotein, lactoferrin-binding protein B (LbpB) is homologous to the structures of the accessory lipoproteins, transferrin-binding protein B (TbpB) and LbpB from the bovine pathogen Moraxella bovis. Docking the LbpB  with lactoferrin reveals extensive binding interactions with the N1 subdomain of lactoferrin. The nature of the interaction precludes apolactoferrin from binding LbpB, ensuring the specificity for iron-loaded lactoferrin, safeguarding proper delivery of iron-bound lactoferrin to the transporter LbpA. The structure also reveals a possible secondary role for LbpB in protecting the bacteria from host defences. Following proteolytic digestion of lactoferrin, a cationic peptide derived from the N-terminus is released. This peptide, called lactoferricin, exhibits potent antimicrobial effects. The docked model of LbpB with lactoferrin reveals that LbpB interacts extensively with the N-terminal lactoferricin region (Brooks et al. 2014). 

Gram-negative bacteria

LbpAB of Neisseria meningitidis

 
1.B.14.2.5TbpA single component transferrin receptor Gram-negative bacteria TbpA of Pasteurella multocida
 
1.B.14.2.6HugA heme receptor/porin

Gram-negative bacteria

HugA of Plesiomonas shigelloides (Q93SS7)

 
1.B.14.2.7

Hemin (Heme)-binding receptor, ShmR (also transports the toxic heme analog, gallium protoporphyrin) (Amarelle et al., 2008).

Bacteria

ShmR of Sinorhizobium meliloti (Q92N43)

 
1.B.14.2.8

The heme-iron (from hemin and hemoglobin) utilization receptor, BhuR (Brickman et al., 2006; Vanderpool and Armstrong, 2004).

Gram-negative bacteria

BhuR of Bordetella pertussis (Q7VSQ4)

 
1.B.14.2.9Probable TonB-dependent receptor NMB0964Y964 of Neisseria meningitidis MC58
 
Examples:

TC#NameOrganismal TypeExample
1.B.14.3.1

BtuB cobalamin receptor (also transports phage C1 DNA across the outer membrane). Two Ca2+ binding sites in BtuB mediate cobalamine binding (Cadieux et al., 2007). Cobalamine uptake into the periplasm is reversible, but efflux is pmf-independent (Cadieux et al., 2007). The 3-d structure is available (PDB#1NQE).  The Ton box and the extracellular substrate binding site are allosterically coupled (bidirectional), and TonB binding may initiate a partial round of transport (Sikora et al. 2016).  Substrate binding to the extracellular surface of the protein triggers the unfolding of an energy coupling motif at the periplasmic surface.  Thus, substrate binding reduces the interaction free energy between certain residues, thereby triggering the unfolding of the energy coupling motif (Lukasik et al. 2007).

Gram-negative bacteria

BtuB of E. coli

 
1.B.14.3.2

TonB-dependent receptor (Bhat et al. 2011).

Proteobacteria

TonB-dependent receptor of Myxococcus xanthus

 
1.B.14.3.3

TonB-dependent receptor (Bhat et al. 2011).

Proteobacteria

TonB receptor of Myxococcus xanthus

 
1.B.14.3.4

TonB-dependent receptor (Bhat et al. 2011).

Proteobacteria

TonB-dependent receptor of Myxococcus xanthus

 
1.B.14.3.5

TonB-dependent receptor (Bhat et al. 2011).

Proteobacteria

TonB-dependent receptor of Myxococcus xanthus

 
1.B.14.3.6

Probable siderophore-specific outer membrane receptor of 869 aas, MxcH

Proteobacteria

MxcH of Stigmatella aurantiaca

 
1.B.14.3.7

TonB-dependent receptor

Proteobacteria

OMR of Shewanella oneidensis

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.4.1

Cu2+-transporting, Cu2+-regulated outer membrane protein C, OprC (Yoneyama and Nakae 1996).

Gram-negative bacteria

OprC of Pseudomonas aeruginosa

 
1.B.14.4.2Cu2+-transporting, outer membrane protein, NosA Gram-negative bacteria NosA of Pseudomonas stutzeri
 
1.B.14.4.3

TonB-dependent receptor/channel for substrate uptake across the outer membrane of 656 aas

Receptor of E. coli

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.5.1

HasR receptor-HasA haemophore heme receptor complex (HasA, an extracellular heme binding protein, binds one heme and transfers it directly to HasR, which uses HasB (2.C.1.1.2) (a TonB homologue) instead of TonB (2.C.1.1.1) for energization) (Benevides-Matos et al., 2008; Izadi-Pruneyre et al., 2006; Lefèvre et al., 2008; Benevides-Matos and Biville, 2010). A signaling domain in HasR interacts with a partially unfolded periplasmic domain of an antisigma factor, HasS, to control transcription by an ECF sigma factor (Malki et al. 2014).  The HasR domain responsible for signal transfer is highly flexible in two stages of signaling, extends into the periplasm at about 70 to 90 A from the HasR beta-barrel and exhibits local conformational changes in response to the arrival of signaling activators (Wojtowicz et al. 2016).

Gram-negative bacteria

HasR-HasA of Serratia marcescens

 
1.B.14.5.2

The heme receptor HxuC (PA1302) serves as a pyocin M4 (Colicin M-type; PaeM4) target at the cellular surface.

HxuC of Pseudomonas aeruginosa

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.6.1

SusC receptor/porin for maltooligosaccharides (up to maltoheptaose). Forms a complex with and functions with SusD (TC# 8.A.46.1.1).  Involved in starch utilization (Shipman et al. 2000; Reeves et al. 1997; Cho and Salyers 2001). 

Gram-negative bacteria

SusC of Bacteroides thetaiotaomicron

 
1.B.14.6.10

DUF4480 putative OMR of 835 aas.

Bacteroidetes

OMR of Capnocytophaga canimorsus

 
1.B.14.6.11

OMR (DUF4480) of 976 aas

Bacteroidetes

OMR of Zobellia galactanivorans

 
1.B.14.6.12

OMR (DUF4480) of 775 aas

Bacteroidetes

OMR of Saprospira grandis

 
1.B.14.6.13

SusC homologue of 940 aas.  Functions with SusD homolgoue TC# 8.A.46.1.2.  

Bacteroidetes

SusC homologue of Bacteroides thetaiotaomicron

 
1.B.14.6.14

Putative porin of 830 aas and 16 predicted TMSs.  The β-barrel domain is the N-terminal ~250 aas which corresponds to the DUF4480 or Peptidase M14NE family in Pfam.  The large hydrophilic C-terminal domain is of unknown function.

Bacteroidetes

Putative porin of Aequorivita sublithincola

 
1.B.14.6.15

TonB-dependent collagenase (proteinase) of 1047 aas (Bhattacharya et al. 2017).  The primary pathogen of the Great Barrier Reef sponge Rhopaloeides odorabile, recently identified as a novel strain (NW4327) of Pseudoalteromonas agarivorans, produces collagenases which degrade R. odorabile skeletal fibers.

Collagenase of Pseudoalteromonas agarivolans NW4327 (a marine sponge parasite)

 
1.B.14.6.2The Omp200 porin complex (consists of Omp121 [an OMR family member] and Omp71 [a protein nonhomologous to other proteins in the databases])Gram-negative bacteriaOmp121/Omp71 complex of Bacteroides fragilis
 
1.B.14.6.3

Outer membrane porin required for intercellular signalling via C-signal (CsgA), Oar (Bhat et al. 2011).

Proteobacteria

Oar of Myxococcus xanthus

 
1.B.14.6.4

TonB-dependent outer membrane porin/receptor, Oar

Proteobacteria

Oar of Stenotrophomonas maltophila

 
1.B.14.6.5

TonB-dependent outer membrane receptor of 792 aas.

Bacteroidetes

TonB receptor of Bacteroides caccae

 
1.B.14.6.6

TonB-dependent receptor of 970 aas

Spirochaetes

TonB receptor of Leptospira interrogans

 
1.B.14.6.7

TonB-dependent receptor

Bacteroidetes

TonB receptor of Pedobacter heparinus

 
1.B.14.6.8

Putative OMR (DUF4480) of 709 aas and one N-terminal TMS.  The first 120 residues show sequence similarity with TC#1.B.14.6.2.

Bacteroidetes

Putative OMR of Bacteroides fragilis

 
1.B.14.6.9

Putative OMR (DUF4480) of 828 aas, and N-terminal TMS and 32 predicted TM β-strands.

Bacteroidetes

Putative OMR of Croceibacter atlanticus

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.7.1

CjrC outer membrane receptor of 753 aas.  It is iron and temperature regulated, and functions with CjrB, a distant TonB homologue (TC# 2.C.1.1.3).  Together these two proteins are required for uptake of colicin J in Shigella and enteroinvasive E. coli strains (Smajs and Weinstock 2001).

Proteobacteria

CjrC of E. coli

 
1.B.14.7.2

Probable TonB-dependent receptor NMB1497

Bacteria

NMB1497 of Neisseria meningitidis 

 
1.B.14.7.3

Probable TonB-dependent receptor HI_1217

Bacteria

HI_1217 of Haemophilus influenzae

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.8.1Putative salicin/arbutin (aromatic β-glucoside) receptor, SalC Gram-negative bacteria SalC of Azospirillum irakense
 
1.B.14.8.2The iron (Fe3+) · pyridine-2,6-bis(thiocarboxylic acid) (PDTC) receptor, PdtK. Functions with the MFS carrier, PdtE (TC #2.A.1.55.1) (Leach and Lewis, 2006).Gram-negative bacteriaPdtK of Pseudomonas putida (ABC68350)
 
1.B.14.8.3Vibriobactin receptor

Bacteria

ViuA of Vibrio cholerae serotype O1

 
1.B.14.8.4

The thiamine receptor (SO2715) (energized by TonB/ExbBD) (Rodionov et al. 2002)

Proteobacteria

SO2715 of Shewanella oneidensis (Q8EDM8)

 
1.B.14.8.5

TonB-dependent receptor of 726 aas.

Proteobacteria

Receptor of Colwellia psychrerythraea

 
1.B.14.8.6

The (thio)quinolobactin receptor, QbsI, of 669 aa

Proteobacteria

QbsI of Pseudomonas fluorescens

 
1.B.14.8.7

FyuA Fe3+-yersiniabactin and pesticin (Psn; a bacteriocin) receptor and uptake protein of 673 aas. It contributes to biofilm formation and infection (Hancock et al., 2008).

Gram-negative bacteria

FyuA of Yersinia enterocolitica (P0C2M9)

 
Examples:

TC#NameOrganismal TypeExample
1.B.14.9.1RhtA Rhizobactin 1021 (siderophore) receptor/porin Gram-negative bacteria RhtA of Sinorhizobium meliloti
 
1.B.14.9.2Acr ferric achromobactin (hydroxycarboxylate siderophore) receptor/porin (Franza et al., 2005)Gram-negative bacteriaAcr of Erwinia chrysanthemi (AAL14566)
 
1.B.14.9.3

The ferric ferrichrome/aerobactin receptor/porin, IutA (Forman et al., 2007)

Bacteria IutA of Yersinia pestis (Q7CGN6)
 
1.B.14.9.4

Putative TonB-dependent heme receptor

Proteobacteria

TonB-dependent heme receptor of Campylobacter jejuni

 
1.B.14.9.5

TonB-dependent receptor of 700 aas, YncD, a probable iron transporter/receptor in the outer membrane.  Deletion of the orthologous yncD genes in Salmonella strains leads to attenuated strains, potentially useful for vaccine development (Xiong et al. 2012; Xiong et al. 2015). Its synthesis is depressed by inclusion of high glucose concentrations in the medium (Yang et al. 2011). YncD is a receptor for a T1-like Escherichia coli phage named vB_EcoS_IME347 (IME347) (Li et al. 2018).

YncD of E. coli

 
1.B.14.9.6

SchT (IutA) is capable of using dihydroxamate xenosiderophores, either ferric schizokinen (FeSK) or a siderophore of the filamentous cyanobacterium Anabaena variabilis ATCC 29413 (SAV), as the sole source of iron in a TonB-dependent manner (Obando S et al. 2018). Functions with the ABC uptake system having the TC# 3.A.1.14.24.

SchT of Synechocystis sp. PCC 6803