Structure of the Cholera Toxin Secretion Channel in Its Closed State

Nat Struct Mol Biol. 2010 Oct;17(10):1226-32. doi: 10.1038/nsmb.1910. Epub 2010 Sep 19.

Abstract

The type II secretion system (T2SS) is a macromolecular complex spanning the inner and outer membranes of Gram-negative bacteria. Remarkably, the T2SS secretes folded proteins, including multimeric assemblies such as cholera toxin and heat-labile enterotoxin from Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. The major outer membrane T2SS protein is the 'secretin' GspD. Cryo-EM reconstruction of the V. cholerae secretin at 19-Å resolution reveals a dodecameric structure reminiscent of a barrel, with a large channel at its center that contains a closed periplasmic gate. The GspD periplasmic domain forms a vestibule with a conserved constriction, and it binds to a pentameric exoprotein and to the trimeric tip of the T2SS pseudopilus. By combining our results with structures of the cholera toxin and T2SS pseudopilus tip, we provide a structural basis for a possible secretion mechanism of the T2SS.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Outer Membrane Proteins / ultrastructure
  • Cholera Toxin / metabolism
  • Conserved Sequence
  • Cryoelectron Microscopy
  • Fimbriae, Bacterial / physiology
  • Image Processing, Computer-Assisted
  • Models, Molecular
  • Molecular Sequence Data
  • Periplasm / chemistry
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Surface Plasmon Resonance
  • Vibrio cholerae / chemistry*
  • Vibrio cholerae / physiology
  • Vibrio cholerae / ultrastructure

Substances

  • Bacterial Outer Membrane Proteins
  • Recombinant Fusion Proteins
  • Cholera Toxin