7Y53

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

7Y53 の概要

• エントリーDOI: 10.2210/pdb7y53/pdb
• EMDBエントリー: 33611
• 分子名称: Derlin-1, Transitional endoplasmic reticulum ATPase, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: erad, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 636319.08

構造登録者

Cao, Y.,Rao, B.,Wang, Q.,Yao, D.,Xia, Y.,Li, W.,Li, S.,Shen, Y. (登録日: 2022-06-16, 公開日: 2023-10-18, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.61 Å)