Figure 4. Model of T6SS action.

IM – inner membrane, PG – peptidoglycan, OM – outer membrane. (a) Assembly - First step is a base plate complex formation that initiates the Hcp tube polymerization. The base plate complex is likely composed of gp25, VgrG and other T6SS proteins that define a bell-shaped cytoplasmic component (black objects) and periplasmic component (brown objects) which together span the inner membrane, peptidoglycan, and outer membrane. Second step is polymerization of the sheath (from VipA/VipB heterodimers) around the Hcp tube in an extended conformation. (b) Extended T6SS apparatus in extended “ready to fire” conformation. The membrane distal end may be capped by an unknown protein or VipAB conformational state. (c) Contraction - Upon an unknown extracellular signal a conformational change in the base plate complex triggers sheath contraction that leads to the translocation (secretion) of the VgrG/Hcp tube complex through effector cell membranes and penetration of adjacent target cell membrane. Translocation of additional effector proteins might then follow using the Hcp tube as a conduit. (d) Disassembly - Contracted sheath is detached and disassembled by ClpV ATPase. VipA/B dimers released are recycled into a new extended T6SS apparatus at either the original or a newly formed base plate complex. In the absence of target cell penetration (see panel c), Hcp and VgrG proteins are released into the extracellular space as secreted proteins.