The BioGRID | PUBLICATION VIEW

	Cell Jul (2006); 126(2):349-59
A luminal surveillance complex that selects misfolded glycoproteins for ER-associated degradation-
Denic V, Quan EM, Weissman JS
Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA-
Abstract: How the ER-associated degradation -ERAD- machinery accurately identifies terminally misfolded proteins is poorly understood- For luminal ERAD substrates, this recognition depends on their folding and glycosylation status as well as on the conserved ER lectin Yos9p- Here we show that Yos9p is part of a stable complex that organizes key components of ERAD machinery on both sides of the ER membrane, including the transmembrane ubiquitin ligase Hrd1p- We further demonstrate that Yos9p, together with Kar2p and Hrd3p, forms a luminal surveillance complex that both recruits nonnative proteins to the core ERAD machinery and assists a distinct sugar-dependent step necessary to commit substrates for degradation- When Hrd1p is uncoupled from the Yos9p surveillance complex, degradation can occur independently of the requirement for glycosylation- Thus, Yos9p-Kar2p-Hrd3p acts as a gatekeeper, ensuring correct identification of terminally misfolded proteins by recruiting misfolded forms to the ERAD machinery, contributing to the interrogation of substrate sugar status, and preventing glycosylation-independent degradation-
[PUBMED: 16873065]