Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones

• Published in: eLife Vol. 9
• Main Authors: Ahmad, Shehryar, Tsang, Kara K, Sachar, Kartik, Quentin, Dennis, Tashin, Tahmid M, Bullen, Nathan P, Raunser, Stefan, McArthur, Andrew G, Prehna, Gerd, Whitney, John C
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 15.12.2020; eLife Sciences Publications, Ltd; eLife Sciences Publications Ltd
• Subjects: Crystals; Escherichia coli - metabolism; Gram-negative bacteria; interbacterial competition; Membrane Proteins - metabolism; Microbiology and Infectious Disease; molecular chaperones; Molecular Chaperones - metabolism; Protein Conformation; Protein Domains; protein transport; Protein Transport - physiology; Proteins; Pseudomonas aeruginosa - metabolism; Salmonella typhimurium - metabolism; Structure; type VI secretion system; Type VI Secretion Systems - metabolism; x-ray crystallography; protein transport; x-ray crystallography; interbacterial competition; type VI secretion system; infectious disease; microbiology; Gram-negative bacteria; molecular chaperones
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.62816

Type VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighboring bacteria. Many effectors harbor N-terminal rans embrane omains (TMDs) implicated in effector translocation across target cell membranes. However, the distribution of these TMD-containing effectors remains unknown. Here, we discover prePAAR, a conserved motif found in over 6000 putative TMD-containing effectors encoded predominantly by 15 genera of Proteobacteria. Based on differing numbers of TMDs, effectors group into two distinct classes that both require 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 Typhimurium and , 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 residues mediate effector-VgrG spike interactions. Taken together, our findings reveal mechanisms of chaperone-mediated stabilization and secretion of two distinct families of T6SS membrane protein effectors.