Structure of a complex of the ATPase SecA and the protein-translocation channel

Abstract

Most proteins are secreted from bacteria by the interplay of the cytoplasmic ATPase SecA and a membrane channel, formed from the heterotrimeric SecY complex. We report crystal structures of SecA bound to the SecY complex, both isolated from different species, with a maximum resolution of 4.5Å. One copy of SecA in its transition state of ATP hydrolysis is bound to one SecY molecule. Both partners undergo major conformational changes upon interaction. The polypeptide-crosslinking domain of SecA makes a large conformational change that could capture the translocation substrate in a “clamp”. Polypeptide movement through the SecY channel could be achieved by the motion of a “two-helix finger” of SecA inside the cytoplasmic funnel of SecY, and the coordinated tightening and widening of SecA’s “clamp”. SecA binding generates a “window” at the lateral gate of the SecY channel and it displaces the plug domain, preparing the channel for signal sequence binding and channel opening.