title: The cotranslational integration of membrane proteins into the phospholipid bilayer is a multistep process.
abstract: During the cotranslational integration of a nascent protein into the endoplasmic reticulum membrane, the transmembrane (TM) sequence moves out of an aqueous pore formed by Sec61alpha, TRAM, and other proteins and into the nonpolar lipid bilayer. Photocross-linking reveals that this movement involves the sequential passage of the TM domain through three different proteinaceous environments: one adjacent to Sec61alpha and TRAM and two adjacent to TRAM that place different restrictions on TM domain movement. In addition, the TM sequence is not allowed to diffuse into the bilayer from the final TRAM-proximal site until translation terminates. Cotranslational integration is therefore linked to translation and occurs via an ordered multistep pathway at an endoplasmic reticulum site that is multilayered both structurally and functionally.
authors.affiliation: Department of Medical Biochemistry & Genetics, Texas A&M University Health Science Center, College Station 77843-1114, USA.
authors.forename: H
authors.initials: H
authors.lastname: Do
authors.forename: D
authors.initials: D
authors.lastname: Falcone
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: D W
authors.initials: DW
authors.lastname: Andrews
authors.forename: A E
authors.initials: AE
authors.lastname: Johnson
mesh_terms: D003432:Cross-Linking Reagents; D005656:Fungal Proteins / Q000502:physiology; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D008970:Molecular Weight; D010743:Phospholipids / Q000502:physiology*; D010777:Photochemistry; D014176:Protein Biosynthesis / Q000502:physiology*; D021382:Protein Sorting Signals / Q000502:physiology; D011691:Puromycin / Q000494:pharmacology; D012343:RNA, Transfer / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D003432:Cross-Linking Reagents; D005656:Fungal Proteins; D008051:Lipid Bilayers; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010743:Phospholipids; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C074282:translocating chain-associating membrane protein (TRAM); D011691:Puromycin; D012343:RNA, Transfer