Structure of the cholera toxin secretion channel in its closed state

Steve L. Reichow, Konstantin V. Korotkov, Wim G.J. Hol, Tamir Gonen

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

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.

Original languageEnglish
Pages (from-to)1226-1232
Number of pages7
JournalNature Structural and Molecular Biology
Volume17
Issue number10
DOIs
StatePublished - Oct 2010

Bibliographical note

Funding Information:
We thank the Murdock Charitable Trust and the Washington Research Foundation for generous support of our cryo-EM facility. We are grateful to J. Sun, M. Gonen, B. Vollmar and S. Turley for contributions to the earlier stages of this work; M. Bagdasarian (Michigan State University) for a VcGspD-containing plasmid; and J. DelaRosa for assistance with protein preparation. We thank A. J. Merz for helpful discussions. We thank N. Korotkova and P. Wallace for discussion of SPR experiments.

Funding Information:
Part of this work was conducted at the University of Washington NanoTech User Facility, a member of the US National Science Foundation (NSF) National Nanotechnology Infrastructure Network (NNIN). This research is supported by the US National Institutes of Health grant AI34501. The Gonen laboratory is supported in part by the Howard Hughes Medical Institute Early Career Scientist program.

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Structure of the cholera toxin secretion channel in its closed state'. Together they form a unique fingerprint.

Cite this