7Y53

The cryo-EM structure of human ERAD retro-translocation complex

Summary for 7Y53

• Entry DOI: 10.2210/pdb7y53/pdb
• EMDB information: 33611
• Descriptor: Derlin-1, Transitional endoplasmic reticulum ATPase, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: erad, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 636319.08

Authors

Cao, Y.,Rao, B.,Wang, Q.,Yao, D.,Xia, Y.,Li, W.,Li, S.,Shen, Y. (deposition date: 2022-06-16, release date: 2023-10-18, Last modification date: 2024-04-03)

Primary citation

Rao, B.,Wang, Q.,Yao, D.,Xia, Y.,Li, W.,Xie, Y.,Li, S.,Cao, M.,Shen, Y.,Qin, A.,Zhao, J.,Cao, Y.
The cryo-EM structure of the human ERAD retrotranslocation complex.
Sci Adv, 9:eadi5656-eadi5656, 2023

PubMed Abstract: Endoplasmic reticulum-associated degradation (ERAD) maintains protein homeostasis by retrieving misfolded proteins from the endoplasmic reticulum (ER) lumen into the cytosol for degradation. The retrotranslocation of misfolded proteins across the ER membrane is an energy-consuming process, with the detailed transportation mechanism still needing clarification. We determined the cryo-EM structures of the hetero-decameric complex formed by the Derlin-1 tetramer and the p97 hexamer. It showed an intriguing asymmetric complex and a putative coordinated squeezing movement in Derlin-1 and p97 parts. With the conformational changes of p97 induced by its ATP hydrolysis activities, the Derlin-1 channel could be torn into a "U" shape with a large opening to the lipidic environment, thereby forming an entry for the substrates in the ER membrane. The EM analysis showed that p97 formed a functional protein complex with Derlin-1, revealing the coupling mechanism between the ERAD retrotranslocation and the ATP hydrolysis activities.

PubMed: 37831771
DOI: 10.1126/sciadv.adi5656

Experimental method

ELECTRON MICROSCOPY (3.61 Å)