The Tip Complex: From Host Cell Sensing to Translocon Formation.

Type III secretion systems are used by some Gram-negative bacteria to inject effector proteins into targeted eukaryotic cells for the benefit of the bacterium. The type III secretion injectisome is a complex nanomachine comprised of four main substructures including a cytoplasmic sorting platform, an envelope-spanning basal body, an extracellular needle and an exposed needle tip complex. Upon contact with a host cell, secretion is induced, resulting in the formation of a translocon pore in the host membrane. Translocon formation completes the conduit needed for effector secretion into the host cell. Control of type III secretion occurs in response to environmental signals, with the final signal being host cell contact. Secretion control occurs primarily at two sites-the cytoplasmic sorting platform, which determines secretion hierarchy, and the needle tip complex, which is critical for sensing and responding to environmental signals. The best-characterized injectisomes are those from Yersinia, Shigella and Salmonella species where there is a wealth of information on the tip complex and the two translocator proteins. Of these systems, the best characterized from a secretion regulation standpoint is Shigella. In the Shigella system, the tip complex and the first secreted translocon both contribute to secretion control and, thus, both are considered components of the tip complex. In this review, all three of these type III secretion systems are described with discussion focused on the structure and formation of the injectisome tip complex and what is known of the transition from nascent tip complex to assembled translocon pore.