6VK1

CryoEM structure of Hrd1/Hrd3 part from Hrd1-Usa1/Der1/Hrd3 complex

Summary for 6VK1

• Entry DOI: 10.2210/pdb6vk1/pdb
• EMDB information: 21220 21221 21222 21223
• Descriptor: ERAD-associated E3 ubiquitin-protein ligase HRD1, ERAD-associated E3 ubiquitin-protein ligase component HRD3 (2 entities in total)
• Functional Keywords: retro-translocation, erad, protein degradation, ubiquitination, protein transport
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 143877.88

Authors

Wu, X.,Rapoport, T.A. (deposition date: 2020-01-18, release date: 2020-04-29, Last modification date: 2024-03-06)

Primary citation

Wu, X.,Siggel, M.,Ovchinnikov, S.,Mi, W.,Svetlov, V.,Nudler, E.,Liao, M.,Hummer, G.,Rapoport, T.A.
Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex.
Science, 368:-, 2020

PubMed Abstract: Misfolded 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.

PubMed: 32327568
DOI: 10.1126/science.aaz2449

Experimental method

ELECTRON MICROSCOPY (3.9 Å)