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

2008; Nature Portfolio; Volume: 455; Issue: 7215 Linguagem: Inglês

10.1038/nature07335

1476-4687

Jochen Zimmer, Yunsun Nam, Tom A. Rapoport,

Bacteriophages and microbial interactions

Most proteins are secreted from bacteria by the interaction of the cytoplasmic SecA ATPase with a membrane channel, formed by the heterotrimeric SecY complex. Here we report the crystal structure of SecA bound to the SecY complex, with a maximum resolution of 4.5 ångström (Å), obtained for components from Thermotoga maritima. One copy of SecA in an intermediate state of ATP hydrolysis is bound to one molecule of the SecY complex. Both partners undergo important conformational changes on interaction. The polypeptide-cross-linking 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 by the coordinated tightening and widening of SecA’s clamp above the SecY pore. 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. Newly synthesized proteins are translocated across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane through an evolutionarily conserved protein conducting channel or translocon known as Sec61 in eukaryotes and SecY in prokaryotes. In bacteria, the SecA ATPase is thought to be the motor for translocation through the SecY channel. Two papers by Tom Rapoport and colleagues report the long-awaited structure of the SecA–SecY complex from bacteria. The structure, reveals major conformational changes between both partners and suggests that SecA uses a two-helix finger to push translocating proteins into SecY's cytoplasmic funnel. Crosslinking studies provide further experimental support for this mechanism. In a third paper, Osamu Nureki and colleagues present a crystal structure of SecY bound to an anti-SecY Fab fragment revealing a pre-open state of the channel. Together these three papers provide novel insights into the path taken by a translocating protein. In News and Views, Anastassios Economou takes stock of where this work leaves current knowledge of this 'astonishing cellular nanomachine'. This study reports the structure of the SecA–SecY complex from bacteria. The structure reveals major conformational changes between both partners and provides novel insights into the path taken by a translocating protein.