6vk3 | pdb_00006vk3
CryoEM structure of Hrd3/Yos9 complex
Structural highlights
Function[OS9_YEAST] Lectin involved in the quality control of the secretory pathway. As a member of the endoplasmic reticulum-associated degradation lumenal (ERAD-L) surveillance system, targets misfolded endoplasmic reticulum lumenal glycoproteins for degradation. The recognition of targets is N-glycan specific.[1] [2] [3] [4] [5] Publication Abstract from PubMedMisfolded luminal endoplasmic reticulum (ER) proteins undergo ER-associated degradation (ERAD-L): They are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome. ERAD-L is mediated by the Hrd1 complex (composed of Hrd1, Hrd3, Der1, Usa1, and Yos9), but the mechanism of retrotranslocation remains mysterious. Here, we report a structure of the active Hrd1 complex, as determined by cryo-electron microscopy analysis of two subcomplexes. Hrd3 and Yos9 jointly create a luminal binding site that recognizes glycosylated substrates. Hrd1 and the rhomboid-like Der1 protein form two "half-channels" with cytosolic and luminal cavities, respectively, and lateral gates facing one another in a thinned membrane region. These structures, along with crosslinking and molecular dynamics simulation results, suggest how a polypeptide loop of an ERAD-L substrate moves through the ER membrane. Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex.,Wu X, Siggel M, Ovchinnikov S, Mi W, Svetlov V, Nudler E, Liao M, Hummer G, Rapoport TA Science. 2020 Apr 24;368(6489). pii: 368/6489/eaaz2449. doi:, 10.1126/science.aaz2449. PMID:32327568[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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