Structural insights into the Type II secretion nanomachine.

The Type II secretion nanomachine transports folded proteins across the outer membrane of Gram-negative bacteria. Recent X-ray crystallography, electron microscopy, and molecular modeling studies provide structural insights into three functionally and spatially connected units of this nanomachine: the cytoplasmic and inner membrane energy-harvesting complex, the periplasmic helical pseudopilus, and the outer membrane secretin. Key advances include cryo-EM reconstruction of the secretin and demonstration that it interacts with both secreted substrates and a crucial transmembrane clamp protein, plus a biochemical and structural explanation of the role of low-abundance pseudopilins in initiating pseudopilus growth. Combining structures and protein interactions, we synthesize a 3D view of the complete complex consistent with a stepwise pathway in which secretin oligomerization defines sites of nanomachine biogenesis.