Type VI secretion and bacteriophage tail tubes share a common assembly pathway

Abstract The Type VI secretion system (T6SS) is a widespread macromolecular structure that delivers protein effectors to both eukaryotic and prokaryotic recipient cells. The current model describes the T6SS as an inverted phage tail composed of a sheath-like structure wrapped around a tube assembled by stacked Hcp hexamers. Although recent progress has been made to understand T6SS sheath assembly and dynamics, there is no evidence that Hcp forms tubes in vivo. Here we show that Hcp interacts with TssB, a component of the T6SS sheath. Using a cysteine substitution approach, we demonstrate that Hcp hexamers assemble tubes in an ordered manner with a head-to-tail stacking that are used as a scaffold for polymerization of the TssB/C sheath-like structure. Finally, we show that VgrG but not TssB/C controls the proper assembly of the Hcp tubular structure. These results highlight the conservation in the assembly mechanisms between the T6SS and the bacteriophage tail tube/sheath. Synopsis image This study shows that the Type VI secretion-associated Hcp protein assembles into tubes in a head-to-tail manner. Hcp tube formation requires the VgrG protein and is necessary for proper polymerization of the TssB/C sheath. The Type VI secretion system (T6SS) protein Hcp assembles tubes in a head-to-tail manner which is required for T6SS sheath polymerization. Hcp1 interacts with the T6SS sheath by directly interacting with the TssB1 subunit. The assembly of the Hcp tubes is controlled by VgrG.