Binding of secretory precursor polypeptides to a translocon subcomplex is regulated by BiP.
The translocation of a secretory precursor protein across the ER membrane comprises three phases: docking of the precursor at the membrane, insertion into the translocation pore, and exit from the pore into the ER lumen. We demonstrate that Sec62p, Sec71p and Sec72p form a translocon subcomplex that engages secretory precursors at the membrane site of the ER translocation machinery. Binding of a precursor to the subcomplex depends on the presence of an intact signal sequence and occurs only in the absence of ATP. In the presence of ATP, the precursor is released from the subcomplex in a reaction mediated by the lumenal hsp70, BiP. This release reaction, which is specific to BiP and requires interaction between BiP and the DnaJ homolog Sec63p, defines a role for BiP and Sec63p early in the ER translocation process.
Lyman
S K
SK
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley 94720, USA.
Schekman
R
R
D000255:Adenosine Triphosphate / Q000502:physiology; D001692:Biological Transport; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D000072235:Mating Factor; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C060153:KAR2 protein, yeast; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; C074213:SEC62 protein, S cerevisiae; C074215:SEC63 protein, S cerevisiae; C084842:SEC66 protein, S cerevisiae; C088668:SEC72 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000072235:Mating Factor; D000255:Adenosine Triphosphate; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C059010:dipeptidyl aminopeptidase B