title: Organization of the native ribosome-translocon complex at the mammalian endoplasmic reticulum membrane.
abstract: In eukaryotic cells, many proteins have to be transported across or inserted into the endoplasmic reticulum membrane during their biogenesis on the ribosome. This process is facilitated by the protein translocon, a highly dynamic multi-subunit membrane protein complex.
  
  
  
  The aim of this review is to summarize the current structural knowledge about protein translocon components in mammals.
  
  
  
  Various structural biology approaches have been used in synergy to characterize the translocon in recent years. X-ray crystallography and cryoelectron microscopy single particle analysis have yielded highly detailed insights into the structure and functional mechanism of the protein-conducting channel Sec61, which constitutes the functional core of the translocon. Cryoelectron tomography and subtomogram analysis have advanced our understanding of the overall structure, molecular organization and compositional heterogeneity of the translocon in a native membrane environment. Tomography densities at subnanometer resolution revealed an intricate network of interactions between the ribosome, Sec61 and accessory translocon components that assist in protein transport, membrane insertion and maturation.
  
  
  
  The protein translocon is a gateway for approximately one third of all synthesized proteins and numerous human diseases are associated with malfunctioning of its components. Thus, detailed insights into the structure and molecular organization of the translocon will not only advance our understanding of membrane protein biogenesis in general, but they can potentially pave the way for novel therapeutic approaches against human diseases.
authors.affiliation: Max-Planck Institute of Biochemistry, Department of Molecular Structural Biology, D-82152 Martinsried, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfeffer
authors.affiliation: Saarland University, Medical Biochemistry and Molecular Biology, D-66421 Homburg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Dudek
authors.affiliation: Saarland University, Medical Biochemistry and Molecular Biology, D-66421 Homburg, Germany. Electronic address: richard.zimmermann@uks.eu.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Max-Planck Institute of Biochemistry, Department of Molecular Structural Biology, D-82152 Martinsried, Germany; Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address: foerster@biochem.mpg.de.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Förster
mesh_terms: D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics* / Q000648:ultrastructure; D000069816:SEC Translocation Channels / Q000235:genetics* / Q000378:metabolism; D014054:Tomography
chemical_list: D000069816:SEC Translocation Channels
keywords: Endoplasmic reticulum; Membrane protein biogenesis; Protein translocon; Ribosome; Structural biology