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

Abstract

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.

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Figure 1: Architecture of the T. maritima SecA–SecYEG complex.
Figure 2: Conformational changes of SecA.
Figure 3: Conformational changes of SecY.
Figure 4: The polypeptide clamp of SecA.
Figure 5: Model for SecA-mediated protein translocation.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Coordinates for the T. maritima SecA–SecYEG complex have been deposited in the RSCB Protein Data Bank (PDB) under the accession code 3DIN.

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Acknowledgements

We thank B. van den Berg and P. Bendapudi for initial experiments with the B. subtilis SecA and T. maritima SecY complex, G. Skiniotis for electron microscopy analysis, W. Li for his help with data processing, the staff at Advanced Photon Source beamlines ID-19 and 24ID and at Brookhaven National Laboratory beamline X29, and the SBGrid consortium at Harvard Medical School. We thank A. Brunger and S. Harrison for comments, and A. Brunger, B. van den Berg, W. Li, A. Osborne and S. Schulman for critical reading of the manuscript. The work was supported by a National Institutes of Health grant. T.A.R. is an HHMI investigator. Y.N. is supported by the Damon Runyon Cancer Research Foundation (DRG-#1953-07).

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Correspondence to Tom A. Rapoport.

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Zimmer, J., Nam, Y. & Rapoport, T. Structure of a complex of the ATPase SecA and the protein-translocation channel. Nature 455, 936–943 (2008). https://doi.org/10.1038/nature07335

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