VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

Significance The type VI secretion system involves multiple strategies for effector delivery via fusion or interaction of effectors to structural components of the phage tail-like structure, the tube component Hcp or spike protein VgrG. However, the detailed mechanisms underlying how diverse VgrG proteins govern effector delivery remains unclear. Here, we report that the divergent C-terminus of VgrG protein is the molecular determinant governing specific effector delivery and is required for interacting with a specific adaptor/chaperone protein that stabilizes and binds directly with the cognate effector. The striking conservation of genetic modules encoding homologous VgrG, a distinct set of potential adaptor/chaperone, and a specific effector in various Proteobacteria strongly suggest a conserved mechanism in type VI effector delivery.