title: Molecular code for transmembrane-helix recognition by the Sec61 translocon.
abstract: Transmembrane alpha-helices in integral membrane proteins are recognized co-translationally and inserted into the membrane of the endoplasmic reticulum by the Sec61 translocon. A full quantitative description of this phenomenon, linking amino acid sequence to membrane insertion efficiency, is still lacking. Here, using in vitro translation of a model protein in the presence of dog pancreas rough microsomes to analyse a large number of systematically designed hydrophobic segments, we present a quantitative analysis of the position-dependent contribution of all 20 amino acids to membrane insertion efficiency, as well as of the effects of transmembrane segment length and flanking amino acids. The emerging picture of translocon-mediated transmembrane helix assembly is simple, with the critical sequence characteristics mirroring the physical properties of the lipid bilayer.
authors: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors: Tara
authors: T
authors: Hessa
authors: Nadja M
authors: NM
authors: Meindl-Beinker
authors: Andreas
authors: A
authors: Bernsel
authors: Hyun
authors: H
authors: Kim
authors: Yoko
authors: Y
authors: Sato
authors: Mirjam
authors: M
authors: Lerch-Bader
authors: IngMarie
authors: I
authors: Nilsson
authors: Stephen H
authors: SH
authors: White
authors: Gunnar
authors: G
authors: von Heijne
mesh_terms: D000818:Animals; D004285:Dogs; D004926:Escherichia coli / Q000201:enzymology; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D010179:Pancreas / Q000166:cytology; D011487:Protein Conformation; D000069816:SEC Translocation Channels; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D012697:Serine Endopeptidases; C026515:type I signal peptidase