A complex of Yos9p and the HRD ligase integrates endoplasmic reticulum quality control into the degradation machinery.
A quality-control system surveys the lumen of the endoplasmic reticulum for terminally misfolded proteins. Polypeptides singled out by this system are ultimately degraded by the cytosolic ubiquitin-proteasome pathway. Key components of both the endoplasmic reticulum quality-control system and the degradation machinery have been identified, but a connection between the two systems has remained elusive. Here, we report an association between the endoplasmic reticulum quality-control lectin Yos9p and Hrd3p, a component of the ubiquitin-proteasome system that links these pathways. We identify designated regions in the luminal domain of Hrd3p that interact with Yos9p and the ubiquitin ligase Hrd1p. Binding of misfolded proteins occurs through Hrd3p, suggesting that Hrd3p recognises proteins that deviate from their native conformation, whereas Yos9p ensures that only terminally misfolded polypeptides are degraded.
Gauss
Robert
R
Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Jarosch
Ernst
E
Sommer
Thomas
T
Hirsch
Christian
C
D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006868:Hydrolysis; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C104622:HRD3 protein, S cerevisiae; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; C495027:Yos9 protein, S cerevisiae; C104621:HRD1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases