Structure of the SecY channel during initiation of protein translocation
View/ Open
Author
Park, Eunyong
Ménétret, Jean-François
Gumbart, James C.
Ludtke, Steven J.
Li, Weikai
Whynot, Andrew
Akey, Christopher W.
Published Version
https://doi.org/10.1038/nature12720Metadata
Show full item recordCitation
Park, Eunyong, Jean-François Ménétret, James C. Gumbart, Steven J. Ludtke, Weikai Li, Andrew Whynot, Tom A. Rapoport, and Christopher W. Akey. 2013. “Structure of the SecY channel during initiation of protein translocation.” Nature 506 (7486): 102-106. doi:10.1038/nature12720. http://dx.doi.org/10.1038/nature12720.Abstract
Many secretory proteins are targeted by signal sequences to a protein-conducting channel, formed by prokaryotic SecY- or eukaryotic Sec61-complexes, and are translocated across the membrane during their synthesis1,2. Crystal structures of the inactive channel show that the SecY subunit of the heterotrimeric complex consists of two halves that form an hourglass-shaped pore with a constriction in the middle of the membrane and a lateral gate that faces the lipid phase3-5. The closed channel has an empty cytoplasmic funnel and an extracellular funnel that is filled with a small helical domain, called the plug. During initiation of translocation, a ribosome–nascent chain complex binds to the SecY/Sec61 complex, resulting in insertion of the nascent chain. However, the mechanism of channel opening during translocation is unclear. Here, we have addressed this question by determining structures of inactive and active ribosome–channel complexes with cryo-electron microscopy. Non-translating ribosome–SecY channel complexes derived from Methanococcus jannaschii or Escherichia coli show the channel in its closed state, and indicate that ribosome binding per se causes only minor changes. The structure of an active E. coli ribosome–channel complex demonstrates that the nascent chain opens the channel, causing mostly rigid body movements of the N- and C-terminal halves of SecY. In this early translocation intermediate, the polypeptide inserts as a loop into the SecY channel with the hydrophobic signal sequence intercalated into the open lateral gate. The nascent chain also forms a loop on the cytoplasmic surface of SecY rather than directly entering the channel.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948209/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:12785886
Collections
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)