TY - JOUR TI - Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones AU - Ahmad, Shehryar AU - Tsang, Kara K AU - Sachar, Kartik AU - Quentin, Dennis AU - Tashin, Tahmid M AU - Bullen, Nathan P AU - Raunser, Stefan AU - McArthur, Andrew G AU - Prehna, Gerd AU - Whitney, John C A2 - Sankaranarayanan, Rajan A2 - Kuriyan, John A2 - Sankaranarayanan, Rajan A2 - Salomon, Dor VL - 9 PY - 2020 DA - 2020/12/15 SP - e62816 C1 - eLife 2020;9:e62816 DO - 10.7554/eLife.62816 UR - https://doi.org/10.7554/eLife.62816 AB - Type VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighboring bacteria. Many effectors harbor N-terminal transmembrane domains (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 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 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. KW - molecular chaperones KW - type VI secretion system KW - x-ray crystallography KW - protein transport KW - Gram-negative bacteria KW - interbacterial competition JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -