Structure and Activity of the Type VI Secretion System

Abstract

The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells. The injection apparatus is composed of a baseplate on which is built a contractile tail tube/sheath complex. The inner tube, topped by the spike complex, is propelled outside of the cell by the contraction of the sheath. The injection system is anchored to the cell envelope and oriented towards the cell exterior by a trans-envelope complex. Effectors delivered by the T6SS are loaded within the inner tube or on the spike complex and can target prokaryotic and/or eukaryotic cells. Here we summarize the structure, assembly, and mechanism of action of the T6SS. We also review the function of effectors and their mode of recruitment and delivery.

FIGURE 1

Schematic representation of the T6SS. The different subunits are labeled, as are the different subcomplexes. IM, inner membrane; OM, outer membrane.

FIGURE 2

Assembly and mechanism of firing of the T6SS. T6SS biogenesis starts with the positioning and assembly of the membrane complex and the assembly of the BP (1). The recruitment and docking of the BP on the membrane complex (2) initiate the TssA-mediated polymerization of the tail tube/sheath tubular structure ( to 5), which is stopped when hitting the opposite membrane by the TagA stopper (5). Sheath contraction propels the tube/spike needle into the target (6). The ClpV ATPase is recruited to the contracted sheath to recycle sheath subunits (6). Needle components, and effectors associated with them, are delivered inside the target (7).

FIGURE 3

Schematic representation of the mechanisms of effector loading. Effectors are depicted as red circles. Specialized effectors are chimeric needle proteins with extensions encoding the effector. Cargo effectors are independent proteins that associate with needle components (Hcp, VgrG, and PAAR). Binding of cargo effectors to needle components could be direct or mediated by adaptor modules that are independent proteins (adaptors) or extensions of VgrG and PAAR (internal adaptors).