Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex

• Published in: Science (American Association for the Advancement of Science) Vol. 368; no. 6489
• Main Authors: Wu, Xudong, Siggel, Marc, Ovchinnikov, Sergey, Mi, Wei, Svetlov, Vladimir, Nudler, Evgeny, Liao, Maofu, Hummer, Gerhard, Rapoport, Tom A.
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 24.04.2020
• Subjects: Adenosine; Adenosine triphosphatase; Binding sites; Biodegradation; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Channels; Computer simulation; Control systems; Crosslinking; Cryoelectron Microscopy; Cytosol; Cytotoxicity; Degradation; Domains; Electron microscopy; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum-Associated Degradation; Gates; Glycan; Glycoproteins; Glycosidases; Grooves; Homeostasis; Homology; Hydrophobicity; Inserts; Intermediates; Lipids; Macromolecules; Mannose; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Microscopy; Molecular dynamics; Molecular Dynamics Simulation; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Phospholipids; Polypeptides; Proteasomes; Protein Domains; Protein Folding; Protein transport; Proteins; Proteolysis; Quality control; Residues; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Substrates; Translocation; Triphosphatase; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - chemistry; Yeast

Misfolded endoplasmic reticulum (ER) proteins are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome in a process known as ER-associated protein degradation (ERAD). ERAD of misfolded luminal ER proteins (ERAD-L) is mediated by the Hrd1 complex, composed of the ubiq...