title: Structure of the native Sec61 protein-conducting channel.
abstract: In mammalian cells, secretory and membrane proteins are translocated across or inserted into the endoplasmic reticulum (ER) membrane by the universally conserved protein-conducting channel Sec61, which has been structurally studied in isolated, detergent-solubilized states. Here we structurally and functionally characterize native, non-solubilized ribosome-Sec61 complexes on rough ER vesicles using cryo-electron tomography and ribosome profiling. Surprisingly, the 9-Å resolution subtomogram average reveals Sec61 in a laterally open conformation, even though the channel is not in the process of inserting membrane proteins into the lipid bilayer. In contrast to recent mechanistic models for polypeptide translocation and insertion, our results indicate that the laterally open conformation of Sec61 is the only conformation present in the ribosome-bound translocon complex, independent of its functional state. Consistent with earlier functional studies, our structure suggests that the ribosome alone, even without a nascent chain, is sufficient for lateral opening of Sec61 in a lipid environment.
authors.affiliation: Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfeffer
authors.affiliation: Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Burbaum
authors.affiliation: Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Unverdorben
authors.affiliation: Department of Biochemistry, Gene Center and Center for integrated Protein Science Munich, University of Munich, Munich D-81377, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Pech
authors.affiliation: Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg D-66421, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Department of Biochemistry, Gene Center and Center for integrated Protein Science Munich, University of Munich, Munich D-81377, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
authors.affiliation: Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Förster
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012270:Ribosomes / Q000378:metabolism; D000069816:SEC Translocation Channels
chemical_list: D008565:Membrane Proteins; D000069816:SEC Translocation Channels