Abstract
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.
Highlights
Bacteria secrete proteins to facilitate interactions with their surrounding environment
Results prePAAR is a motif found in transmembrane domains (TMDs)-containing effectors that interact with effector-associated gene (Eag) chaperones
We previously showed that EagT6 interacts with the N-terminal TMDs of Tse6, an observation that led us to hypothesize a general role for Eag chaperones in ‘solubilizing’ hydrophobic TMDs of effectors in the aqueous environment of the cytoplasm so they can be loaded into the T6SS apparatus (Figure 1B; Quentin et al, 2018)
Summary
Bacteria secrete proteins to facilitate interactions with their surrounding environment. In Gram-negative bacteria, the transport of proteins across cellular membranes often requires the use of specialized secretion apparatuses found within the cell envelope. One such pathway is the type VI secretion system (T6SS), which in many bacterial species functions to deliver antibacterial effector proteins from the cytoplasm directly into an adjacent bacterial cell via a one-step secretion event (Russell et al, 2011). A critical step that precedes type VI secretion is the selective recruitment of effectors to the T6SS apparatus. Recent work has shown that for many effectors this process requires chaperone proteins, which are thought to maintain effectors in a ‘secretion-competent’ state (Unterweger et al, 2017). To-date, no molecular-level evidence exists to support this idea
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