1.B.38 The Treponema Porin Major Surface Protein (TP-MSP) Family

MSP is a 53 kDa (474 aa) surface antigen in the outer sheath of Treponema denticola. It is an adhesin, but additionally it has been purified to homogeneity and reconstituted in black lipid membranes where it showed channel activity (Egli et al., 1993). It also induces channel activity in HeLa cell membranes (Mathers et al., 1996). The channel had a single conductance of 1.8 nS in 0.1 M KCl (estimated pore diameter of 3.4 nm), the largest porin channel documented in 1996. Electron microscopy suggested a regular hexagonal array in the membrane. Homologues are found in other Treponema species.

The transport reaction catalyzed by MSP is:

ions (non-selective)(periplasm) ions (out)



Anand A., LeDoyt M., Karanian C., Luthra A., Koszelak-Rosenblum M., Malkowski MG., Puthenveetil R., Vinogradova O. and Radolf JD. (2015). Bipartite Topology of Treponema pallidum Repeat Proteins C/D and I: OUTER MEMBRANE INSERTION, TRIMERIZATION, AND PORIN FUNCTION REQUIRE A C-TERMINAL beta-BARREL DOMAIN. J Biol Chem. 290(19):12313-31.

Anand, A., A. Luthra, M.E. Edmond, M. Ledoyt, M.J. Caimano, and J.D. Radolf. (2013). The major outer sheath protein (Msp) of Treponema denticola has a bipartite domain architecture and exists as periplasmic and outer membrane-spanning conformers. J. Bacteriol. 195: 2060-2071.

Cameron, E.A., M.A. Maynard, C.J. Smith, T.J. Smith, N.M. Koropatkin, and E.C. Martens. (2012). Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism. J. Biol. Chem. 287: 34614-34625.

Cho, K.H. and A.A. Salyers. (2001). Biochemical analysis of interactions between outer membrane proteins that contribute to starch utilization by Bacteroides thetaiotaomicron. J. Bacteriol. 183: 7224-7230.

Egli, C., W.K. Leung, K.H. Muller, R.E. Hancock, and B.C. McBride. (1993). Pore-forming properties of the major 53-kilodalton surface antigen from the outer sheath of Treponema denticola. Infect. Immun. 61: 1694-1699.

Foley, M.H., E.C. Martens, and N.M. Koropatkin. (2018). SusE facilitates starch uptake independent of starch binding in B. thetaiotaomicron. Mol. Microbiol. 108: 551-566.

Giacani, L., S.L. Brandt, M. Puray-Chavez, T.B. Reid, C. Godornes, B.J. Molini, M. Benzler, J.S. Hartig, S.A. Lukehart, and A. Centurion-Lara. (2012). Comparative investigation of the genomic regions involved in antigenic variation of the TprK antigen among treponemal species, subspecies, and strains. J. Bacteriol. 194: 4208-4225.

Joglekar, P., E.D. Sonnenburg, S.K. Higginbottom, K.A. Earle, C. Morland, S. Shapiro-Ward, D.N. Bolam, and J.L. Sonnenburg. (2018). Genetic Variation of the SusC/SusD Homologs from a Polysaccharide Utilization Locus Underlies Divergent Fructan Specificities and Functional Adaptation in Strains. mSphere 3:.

Kumar, S., M.J. Caimano, A. Anand, A. Dey, K.L. Hawley, M.E. LeDoyt, C.J. La Vake, A.R. Cruz, L.G. Ramirez, L. Paštěková, I. Bezsonova, D. Šmajs, J.C. Salazar, and J.D. Radolf. (2018). Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of subsp. , the Syphilis Spirochete. MBio 9:.

Mathers, D.A., W.K. Leung, J.C. Fenno, Y. Hong, and B.C. McBride. (1996). The major surface protein complex of Treponema denticola depolarizes and induces ion channels in HeLa cell membranes. Infect. Immun. 64: 2904-2910.

Puthenveetil, R., S. Kumar, M.J. Caimano, A. Dey, A. Anand, O. Vinogradova, and J.D. Radolf. (2017). The major outer sheath protein forms distinct conformers and multimeric complexes in the outer membrane and periplasm of Treponema denticola. Sci Rep 7: 13260.

Reid, T.B., B.J. Molini, M.C. Fernandez, and S.A. Lukehart. (2014). Antigenic variation of TprK facilitates development of secondary syphilis. Infect. Immun. 82: 4959-4967.

Shipman, J.A., J.E. Berleman, and A.A. Salyers. (2000). Characterization of four outer membrane proteins involved in binding starch to the cell surface of Bacteroides thetaiotaomicron. J. Bacteriol. 182: 5365-5372.


TC#NameOrganismal TypeExample

Large non-selective MSP porin of 574 aas, with short lived large ion conduction (Mathers et al. 1996). Contains  MOSP_N and MOSP_C domains which exists as periplasmic hydrophilic monomers and trimeric porins, respectively. MOSP_C, destined for the OM, follows the canonical BAM pathway, but formation of a stable periplasmic conformer of MOSP_N involves an export-related, folding pathway not present in E. coli (Puthenveetil et al. 2017).

Spirochetes (Treponema species)

Msp of Treponema denticola


SusD protein of 570 aas and 1 N-terminal TMS (Joglekar et al. 2018).

SusD of Bacteroides thetaiotaomicron


Treponema repeat protein K (TprK), an outer membrane surface exposed variable antigen which plays a role in immune evasion and persistence (Giacani et al. 2012; Reid et al. 2014).


TprK of Treponema pallidum


Repeat protein, TprEb


Repeat protein, TprEb


Major outer membrane sheath protein, Msp or MOSP, of 543 aas.  Msp has a bipartide structure and exists as periplasmic and outer membrane-integrated trimeric conformers (Anand et al. 2013).  The N-terminal domain (residues 77 - 286) does not insert into the membrane, but the C-terminal domain (residues 332 - 543) does to form pores (Anand et al. 2013).  It resembles the surface exposed variable antigen, TprK (Giacani et al. 2012) which plays roles in immune evasion and persistence.  MOSP is one of its principal cell surface virulence determinants. Bioinformatics predicts that MOSP consists of N- and C-terminal domains, MOSPN and MOSPC. Biophysical analysis of constructs refolded in vitro demonstrated that MOSPC, which has porin activity, forms amphiphilic trimers, while MOSPN forms an extended hydrophilic monomer (Puthenveetil et al. 2017). It is a also a pore-forming cytotoxin that inserts into animal cell membranes (see TC# 1.C.128.1.1), and is a constituent of the outer membrane lipoprotein-protease complex of the Dentilisin Family (TC# 9.B.355).


Major outer sheath protein, Msp, of Treponema denticola


Outer membrane bipartite trimeric porin of 598 aas with an N-terminal MOSPN domain (in the periplasm), and a C-terminal MOSPC domain (cell surface localized), TprC/TprD.  The MOSPN domain confers envelope integrity by anchoring the C-terminal porin domain to periplasmic structural constituents (Anand et al. 2015). Selection pressures exerted within human populations drive T. pallidum subsp. pallidum TrpC diversity by mutation of loop regions and by recombination(Kumar et al. 2018).


TprC of Treponema pallidum


Outer membrane trimeric porin, TprI of 598 aas with a structure similar to that of TprC (TC# 1.B.38.1.5) (Anand et al. 2015).


TprI of Treponema pallidum


SusD of 502 aas and 1 N-terminal TMS.

SusD of Bacteroides fragilis


Uncharacterized major outer membrane protein of 511 aas and 1 N-terminal TMS.

UP of Treponema vincentii


Outer membrane pore-forming TprA protein of 607 aas. This protein is 91% identical to the TprA protein of T. pallidum.

TprA of Treponema paraluiscuniculi


TC#NameOrganismal TypeExample

Putative outer membrane protein of 460 aas. Shows some sequence similarity to autotransporters (1.B.40)


OMP of Spirochaeta thermophila


Putative outer membrane protein of 446 aas.  Shows some sequence similiarity to autotransporters (1.B.40)


OMP of Spirochaeta thermophila


Uncharacterized porin of 389 aas and 1 N-terminal TMS.

UP of Spirochaetae bacterium


Uncharacterized protein of 469 aas.

UP of Spirochaeta perfilievii


TC#NameOrganismal TypeExample

Putative sheath protein of 520 aas with 14 putative β-TMSs at the N-terminus and a fairly long C-terminal extension.


Putative sheath protein of Treponema brennaborense


Putative outer membrane protein of 575 aas and 24 putative β-TMSs, MspA


MspA of Treponema maltophilum


Putative outer membrane protein of 590 aas and 22 putative β-TMSs.


OMP of Treponema lecithinolyticum


TC#NameOrganismal TypeExample

Outer membrane maltooligosaccharide uptake protein, SusE, of 387 aas and 1 N-terminal TMS.  It forms a complex with the SusC porin (TC# 1.B.14.6.1), the SusD porin (TC# 1.B.38.1.10), the SusF porin (TC# 1.B.38.4.2) and SusG (α-amylase; TC# 8.A.9.1.3) in the outer membrane (Foley et al. 2018).  The complex binds starch and maltooligosaccharides (Cho and Salyers 2001).

OMP of Bacteroides thetaiotaomicron


Outer membrane protein, SusF, of 485 aas and 1 N-terminal TMS.  The protein has an N-terminal DUF5115 domain followed by two C-terminal CBM-SusEF-like domains. SusF mediates starch-binding (or maltooligosaccharde-binding) before transport into the periplasm for further degradation. SusE and SusF do not constitute the major starch-binding proteins in the starch degradative pathway. SusF has lower affinity for starch compared to SusE (Shipman et al. 2000). The 3-d structure of the complex has been determined (Cameron et al. 2012). The SusCDEFG complex in the outer membrane is described in more detail in TC# 1.B.38.4.1 (Foley et al. 2018).

OMP, SusF, of Bacteroides thetaiotaomicron


SusE/F homologue of 347 aas and 1 N-terminal TMS.

AusE of Pontibacter lucknowensis


Uncharacterized DUF5115 domain-containing protein of 477 aas and 1 N-terminal TMS.

UP of Chryseobacterium chaponense


Uncharacterized SusD homologue of 531 aas and 1 N-terminal TMS.

SusD homologue of Phaeodactylibacter xiamenensis