title: Yos9p assists in the degradation of certain nonglycosylated proteins from the endoplasmic reticulum.
abstract: The HRD ubiquitin ligase recognizes and ubiquitylates proteins of the endoplasmic reticulum that display structural defects. Here, we apply quantitative proteomics to characterize the substrate spectrum of the HRD complex. Among the identified substrates is Erg3p, a glycoprotein involved in sterol synthesis. We characterize Erg3p and demonstrate that the elimination of Erg3p requires Htm1p and Yos9p, two proteins that take part in the glycan-dependent turnover of aberrant proteins. We further show that the HRD ligase also mediates the breakdown of Erg3p and CPY* engineered to lack N-glycans. The degradation of these nonglycosylated substrates is enhanced by a mutant variant of Yos9p that has lost its affinity for oligosaccharides, indicating that Yos9p has a previously unrecognized role in the quality control of nonglycosylated proteins.
authors: Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
authors: Laura A
authors: LA
authors: Jaenicke
authors: Holger
authors: H
authors: Brendebach
authors: Matthias
authors: M
authors: Selbach
authors: Christian
authors: C
authors: Hirsch
mesh_terms: D002268:Carboxypeptidases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C495027:Yos9 protein, S cerevisiae; D010088:Oxidoreductases; C039306:sterol delta-5 desaturase; C104621:HRD1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D002268:Carboxypeptidases; C520242:CPY protein, S cerevisiae