Type VI secretion system (T6SS) appears to be confined to Proteobacteria. It is important for bacterial pathogenesis, but it is also found in non-pathogenic bacteria, suggesting that T6SS involvement is not limited to virulence []. T6SS was identified in Vibrio cholerae []and Pseudomonas aeruginosa [], and exports Hcp (Haemolysin-Coregulated Protein) and a class of proteins named Vgr (Val-Gly Repeats). In addition to Vgr and Hcp proteins, T6SS is characterised by the presence of an AAA+ Clp-like ATPase and of two additional genes icmF and dotU, encoding homologues of T4SS stabilising proteins []. Type VI secretion system spike protein VgrG2a and VgrG2b are homologous to (gp27)3-(gp5)3 phage-tail proteins, which is followed by a domain of unknown function (DUF2345). Unlike VgrG2a, VgrG2b belongs to a subclass of VgrG proteins, called evolved VgrGs that have an additional C-terminal extension with a putative zinc-dependent metallopeptidase domain. VrgG2b acts directly as an effector and promotes internalization by interacting with the host gamma-tubulin ring complex []. It also elicits toxicity also in the bacterial periplasm and disrupts bacterial cell morphology. This toxicity is counteracted by a cognate immunity protein []. In addition, it allows the delivery of the Tle3 antibacterial toxin to target cells where it exerts its toxicity [].This entry represents DUF2345, which is found in the C-terminal region of VgrG2a/b from Pseudomonas aeruginosa. This domain, present in both proteins, folds as a β-prism [, ].
