Year: 2014
Type: article
Abstract: 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. 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.
Source: PLoS Pathogens
Authors: Tara L. Archuleta, Benjamin W. Spiller
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Energy, American Heart Association, Michigan Economic Development Corporation, Vanderbilt University, National Institutes of Health, Office of Science, Michigan Technology Tri-Corridor, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, G1505794299, G1664757510, G1947107004, G2101401529, G2287611682, G262962599, G2887060908, G2896567508, G3075337988, G3329398301, G340565428, Directed evolution of inhibitors of anthrax toxin, G3962056133, Integrative Training in Therapeutic Discovery, G416541740, CopN mechanism as a key to understanding Type Three Secretion in bacteria, G4773269573, G498139845, G5106849484, G5607048534, G5786433276, G5906309288, G6101244626, G6848031779, G6918803902, G7147508703, G7368700025, G9000162071, G969889393, G993149817
OpenAlex ID: W2076715530