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Title: A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

Journal Article · · PLoS Pathogens
 [1];  [1];  [2]
  1. Vanderbilt Univ. School of Medicine, Nashville, TN (United States)
  2. Osaka Univ. (Japan)

Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1164176
Journal Information:
PLoS Pathogens, Vol. 10, Issue 11; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

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Cited By (6)

Novel insights into the mechanism of SepL-mediated control of effector secretion in enteropathogenic Escherichia coli journal December 2017
Assembly, structure, function and regulation of type III secretion systems journal April 2017
Insight into microtubule nucleation from tubulin-capping proteins journal April 2019
Steps for Shigella Gatekeeper Protein MxiC Function in Hierarchical Type III Secretion Regulation journal December 2016
Type Three Secretion System in Attaching and Effacing Pathogens journal October 2016
Insight into microtubule nucleation from tubulin-capping proteins text January 2019