The type II secretion system: biogenesis, molecular architecture and mechanism

Key Points The type II secretion system (T2SS) is a double-membrane-spanning protein secretion system composed of 12–15 different general secretory pathway (Gsp) proteins that are present in various copy numbers. It is found in a large number of pathogenic and non-pathogenic Gram-negative bacteria. The T2SSs of different species secrete a wide variety of folded exoproteins of different functions, shapes, sizes and quaternary structures. The T2SS secretion signal is still unknown, but it has been suggested that β-complementation is a feature of this signal. The T2SS contains several subassemblies: the outer-membrane secretin, the periplasmic pseudopilus and a cytoplasmic ATPase all interact with components of the inner-membrane platform. Crystal structures have been determined for the majority of T2SS domains, together with binary complexes showing the interaction of the inner-membrane platform with the ATPase and with the outer-membrane secretin, and a ternary complex of three pseudopilins forming the tip of the pseudopilus. Electron microscopy studies indicate that the outer-membrane complex is dodecameric, and indirect evidence suggests that the ATPase is hexameric. The stoichiometry of the inner-membrane platform is still largely a mystery. The current hypothesis regarding the mode of T2SS action is that an exoprotein is captured in the periplasmic vestibule of the outer-membrane secretin, possibly assisted by the inner-membrane protein GspC, and that this induces ATP hydrolysis by the ATPase, leading to conformational changes in the ATPase and the inner-membrane platform. This, in turn, results in elongation of the pseudopilus, which then functions as a piston, opening the periplasmic gate in the outer-membrane secretin to form a channel and then expelling the exoprotein. Many Gram-negative bacteria use type II secretion systems (T2SSs) to translocate a range of proteins across the outer membrane from the periplasm. In this Review, Hol and colleagues describe how recent structural and biochemical studies have provided insights into the biogenesis and architecture of T2SSs and the mechanism by which they function. Many Gram-negative bacteria use the sophisticated type II secretion system (T2SS) to translocate a wide range of proteins from the periplasm across the outer membrane. The inner-membrane platform of the T2SS is the nexus of the system and orchestrates the secretion process through its interactions with the periplasmic filamentous pseudopilus,