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Structural Basis for Effector Transmembrane Domain Recognition by Type VI Secretion System Chaperones
Author(s) -
Whitney John,
Ahmad Shehryar,
Tsang Kara,
Sachar Kartik,
McArthur Andrew,
Prehna Gerd
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01667
Subject(s) - effector , chaperone (clinical) , secretion , transmembrane domain , microbiology and biotechnology , biology , transmembrane protein , transport protein , type three secretion system , computational biology , biochemistry , virulence , membrane , receptor , gene , medicine , pathology
Type VI secretion systems facilitate the delivery of antibacterial effector proteins between neighbouring Gram‐negative bacteria. A subset of these effectors harbour N‐terminal transmembrane domains (TMDs) implicated in effector translocation across the target cell membrane. However, the abundance and distribution of these TMD‐containing effectors has remained unknown. Here, we report the discovery of prePAAR, a conserved motif found in over 6,000 putative TMD‐containing effectors. Based on their differing sizes and number of TMDs these effectors fall into two distinct classes that are unified by their requirement for a member of the Eag family of T6SS chaperones for export. Co‐crystal structures of class I and class II effector TMD‐chaperone complexes from Salmonella Typhimurium and Pseudomonas aeruginosa , respectively, reveals that Eag chaperones mimic transmembrane helical packing to stabilize effector TMDs. In addition to participating in the chaperone‐TMD interface, we find that prePAAR functions to facilitate proper folding of the downstream PAAR domain, which is required for effector interaction with the T6SS spike. Taken together, our findings define the mechanism of chaperone‐assisted secretion of a widespread family of T6SS membrane protein effectors.