Figure 6.

Hierarchy and timing of substrate secretion. (1) In the early phase, PrgI and PrgJ are translocated to build up the inner rod and needle filament; (2) then the translocases are secreted to form the tip (SipD) at the distal end of the needle filament, which connects to the host cell membrane-embedded translocon (SipB, SipC) and establishes a physical connection between the bacterium and the host cell. (3) The effector proteins (late substrates) are translocated from the bacterial to the eukaryotic cytoplasm. Assisted by their cognate chaperones, they interact with the sorting platform (SpaO, OrgA and OrgB) and are then specifically recognized by the T3-associated ATPase (InvC). (4) ATP binding and hydrolysis are required to release the chaperone from its substrate and to unfold the substrate. The unfolded substrate is then believed to travel the secretion pathway through the inner rod and the needle filament (5) into the host cell cytoplasm. OM, outer membrane; P, periplasm; IM, inner membrane; HM, host cell membrane.