Organization of the native ribosome–translocon complex at the mammalian endoplasmic reticulum membrane

• Published in: Biochimica et biophysica acta Vol. 1860; no. 10; pp. 2122 - 2129
• Main Authors: Pfeffer, Stefan, Dudek, Johanna, Zimmermann, Richard, Förster, Friedrich
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2016
• Subjects: biogenesis; Cell Membrane - genetics; Cell Membrane - metabolism; chemical structure; cryo-electron microscopy; Crystallography, X-Ray; Endoplasmic reticulum; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - metabolism; eukaryotic cells; human diseases; Humans; mammals; Membrane protein biogenesis; protein synthesis; Protein translocon; Protein Transport - genetics; Ribosome; ribosomes; Ribosomes - genetics; Ribosomes - ultrastructure; SEC Translocation Channels - genetics; SEC Translocation Channels - metabolism; Structural biology; Tomography; X-ray diffraction; Ribosome; RNC; SPC; Protein translocon; EM; TRAP; Membrane protein biogenesis; ER; TRAM; ES; SRP; OST; CET; Endoplasmic reticulum; FIB; Structural biology; SR
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.06.024

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. [Display omitted] •Advances in cryo-EM have propelled structural analysis of the translocon.•Sec61, TRAP and OST constitute the mammalian translocon core.•An intricate network of interactions organizes the ribosome–translocon complex.•The translocon is characterized by a high degree of compositional heterogeneity.