Abstract
Many proteins are translocated across, or integrated into, membranes. Both functions are fulfilled by the 'translocon/translocase', which contains a membrane-embedded protein-conducting channel (PCC) and associated soluble factors that drive translocation and insertion reactions using nucleotide triphosphates as fuel. This perspective focuses on reinterpreting existing experimental data in light of a recently proposed PCC model comprising a front-to-front dimer of SecY or Sec61 heterotrimeric complexes. In this new framework, we propose (i) a revised model for SRP-SR–mediated docking of the ribosome–nascent polypeptide to the PCC; (ii) that the dynamic interplay between protein substrate, soluble factors and PCC controls the opening and closing of a transmembrane channel across, and/or a lateral gate into, the membrane; and (iii) that co- and post-translational translocation, involving the ribosome and SecA, respectively, not only converge at the PCC but also use analogous mechanisms for coordinating protein translocation.
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Acknowledgements
We apologize to those colleagues whose work is not cited due to space restrictions. This work was supported by the Howard Hughes Medical Institute, the National Science Foundation and the US National Institutes of Health (to J.F.) and by the Council for Chemical Sciences that is subsidized by the Dutch Organization for the Advancement of Scientific Research (to A.D.).
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Supplementary Fig. 1
Architectural features of monomeric and dimeric SecA. (PDF 422 kb)
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Mitra, K., Frank, J. & Driessen, A. Co- and post-translational translocation through the protein-conducting channel: analogous mechanisms at work?. Nat Struct Mol Biol 13, 957–964 (2006). https://doi.org/10.1038/nsmb1166
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DOI: https://doi.org/10.1038/nsmb1166
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