title: Signal sequence recognition in posttranslational protein transport across the yeast ER membrane.
abstract: We have analyzed how the signal sequence of prepro-alpha-factor is recognized during the first step of posttranslational protein transport into the yeast endoplasmic reticulum. Cross-linking studies indicate that the signal sequence interacts in a Kar2p- and ATP-independent reaction with Sec61p, the multispanning membrane component of the protein-conducting channel, by intercalation into transmembrane domains 2 and 7. While bound to Sec61p, the signal sequence forms a helix that is contacted on one side by Sec62p and Sec71p. The binding site is located at the interface of the protein channel and the lipid bilayer. Signal sequence recognition in cotranslational translocation in mammals appears to occur similarly. These results suggest a general mechanism by which the signal sequence could open the channel for polypeptide transport.
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Plath
authors.forename: W
authors.initials: W
authors.lastname: Mothes
authors.forename: B M
authors.initials: BM
authors.lastname: Wilkinson
authors.forename: C J
authors.initials: CJ
authors.lastname: Stirling
authors.forename: T A
authors.initials: TA
authors.lastname: Rapoport
mesh_terms: D001692:Biological Transport / Q000502:physiology; D003432:Cross-Linking Reagents / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000032:analysis / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D016296:Mutagenesis / Q000502:physiology; D010649:Phenylalanine / Q000031:analogs & derivatives; D010777:Photochemistry; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D021382:Protein Sorting Signals / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D003432:Cross-Linking Reagents; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C060153:KAR2 protein, yeast; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D010649:Phenylalanine; D008239:Lysine