Bipartite Topology of Treponema pallidum Repeat Proteins C/D and I: OUTER MEMBRANE INSERTION, TRIMERIZATION, AND PORIN FUNCTION REQUIRE A C-TERMINAL β-BARREL DOMAIN

J Biol Chem. 2015 May 8;290(19):12313-31. doi: 10.1074/jbc.M114.629188. Epub 2015 Mar 24.

Abstract

We previously identified Treponema pallidum repeat proteins TprC/D, TprF, and TprI as candidate outer membrane proteins (OMPs) and subsequently demonstrated that TprC is not only a rare OMP but also forms trimers and has porin activity. We also reported that TprC contains N- and C-terminal domains (TprC(N) and TprC(C)) orthologous to regions in the major outer sheath protein (MOSP(N) and MOSP(C)) of Treponema denticola and that TprC(C) is solely responsible for β-barrel formation, trimerization, and porin function by the full-length protein. Herein, we show that TprI also possesses bipartite architecture, trimeric structure, and porin function and that the MOSP(C)-like domains of native TprC and TprI are surface-exposed in T. pallidum, whereas their MOSP(N)-like domains are tethered within the periplasm. TprF, which does not contain a MOSP(C)-like domain, lacks amphiphilicity and porin activity, adopts an extended inflexible structure, and, in T. pallidum, is tightly bound to the protoplasmic cylinder. By thermal denaturation, the MOSP(N) and MOSP(C)-like domains of TprC and TprI are highly thermostable, endowing the full-length proteins with impressive conformational stability. When expressed in Escherichia coli with PelB signal sequences, TprC and TprI localize to the outer membrane, adopting bipartite topologies, whereas TprF is periplasmic. We propose that the MOSP(N)-like domains enhance the structural integrity of the cell envelope by anchoring the β-barrels within the periplasm. In addition to being bona fide T. pallidum rare outer membrane proteins, TprC/D and TprI represent a new class of dual function, bipartite bacterial OMP.

Keywords: Electron Microscopy (EM); Microbial Pathogenesis; Outer Membrane; Outer Membrane Proteins; Porins; Small Angle X-ray Scattering (SAXS); Syphilis; Treponema pallidum; X-ray Scattering; beta-Barrel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Circular Dichroism
  • Cloning, Molecular
  • Escherichia coli / metabolism
  • Hot Temperature
  • Liposomes / chemistry
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Nanoparticles / chemistry
  • Octoxynol
  • Peptides / chemistry
  • Periplasm / metabolism
  • Polyethylene Glycols / chemistry
  • Porins / chemistry*
  • Protein Denaturation
  • Protein Multimerization
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Scattering, Radiation
  • Syphilis / microbiology
  • Temperature
  • Treponema pallidum / chemistry*

Substances

  • Bacterial Outer Membrane Proteins
  • Liposomes
  • Peptides
  • Porins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Octoxynol
  • Nonidet P-40