title: Protein transport into the human ER and related diseases, Sec61-channelopathies.
abstract: Protein transport into the human endoplasmic reticulum (ER) is relevant to the biogenesis of most soluble and membrane proteins of organelles, which are involved in endo- or exo-cytsosis. It involves amino-terminal signal peptides in the precursor polypeptides and various transport components in the cytosol plus the ER, and can occur co- or post-translationally. The two mechanisms merge at the level of the ER membrane, specifically at the level of the heterotrimeric Sec61 complex, which forms a dynamic polypeptide-conducting channel in the ER membrane. Since the mammalian ER is also the main intracellular calcium storage organelle, and the Sec61 complex is calcium permeable, the Sec61 complex is tightly regulated in its equilibrium between the closed and open conformations, or "gated", by ligands, such as signal peptides of the transport substrates and the ER lumenal Hsp70-type molecular chaperone BiP. Furthermore, BiP binding to the incoming polypeptide contributes to the efficiency and unidirectionality of transport. Recent insights into the structure and dynamic equilibrium of the Sec61 complex have various mechanistic as well as medical implications.
authors.affiliation: Medical Biochemistry & Molecular Biology, Saarland University, Building 44, Kirrbergerstr, D-66421 Homburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Haßdenteufel
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Klein
authors.forename: Armin
authors.initials: A
authors.lastname: Melnyk
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
mesh_terms: D053447:Channelopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000235:genetics; D000069816:SEC Translocation Channels
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels
keywords: Sec61 complex; Sec61-channelopathies; biogenèse des protéines membranaires; canalopathies liées à Sec61; complexe Sec61; endoplasmic reticulum; membrane protein biogenesis; protein transport; réticulum endoplasmique; transport des protéines