title: Structure of the mammalian ribosome-Sec61 complex to 3.4 Å resolution.
abstract: Cotranslational protein translocation is a universally conserved process for secretory and membrane protein biosynthesis. Nascent polypeptides emerging from a translating ribosome are either transported across or inserted into the membrane via the ribosome-bound Sec61 channel. Here, we report structures of a mammalian ribosome-Sec61 complex in both idle and translating states, determined to 3.4 and 3.9 Å resolution. The data sets permit building of a near-complete atomic model of the mammalian ribosome, visualization of A/P and P/E hybrid-state tRNAs, and analysis of a nascent polypeptide in the exit tunnel. Unprecedented chemical detail is observed for both the ribosome-Sec61 interaction and the conformational state of Sec61 upon ribosome binding. Comparison of the maps from idle and translating complexes suggests how conformational changes to the Sec61 channel could facilitate translocation of a secreted polypeptide. The high-resolution structure of the mammalian ribosome-Sec61 complex provides a valuable reference for future functional and structural studies.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address: voorhees@mrc-lmb.cam.ac.uk.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Voorhees
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Israel S
authors.initials: IS
authors.lastname: Fernández
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: Sjors H W
authors.initials: SH
authors.lastname: Scheres
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address: rhegde@mrc-lmb.cam.ac.uk.
authors.forename: Ramanujan S
authors.initials: RS
authors.lastname: Hegde
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D000069816:SEC Translocation Channels; D013552:Swine
chemical_list: D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D012343:RNA, Transfer