8TAR

APC/C-CDH1-UBE2C-Ubiquitin-CyclinB-NTD

8TAR の概要

• エントリーDOI: 10.2210/pdb8tar/pdb
• EMDBエントリー: 41140
• 分子名称: Anaphase-promoting complex subunit 1, Anaphase-promoting complex subunit 10, Anaphase-promoting complex subunit 13, ... (18 entities in total)
• 機能のキーワード: e3 ring ligase, ubiquitin ligase, ligase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 1228921.53

構造登録者

Bodrug, T.,Welsh, K.A.,Bolhuis, D.L.,Paulakonis, E.,Martinez-Chacin, R.C.,Liu, B.,Pinkin, N.,Bonacci, T.,Cui, L.,Xu, P.,Roscow, O.,Amann, S.J.,Grishkovskaya, I.,Emanuele, M.J.,Harrison, J.S.,Steimel, J.P.,Hahn, K.M.,Zhang, W.,Zhong, E.,Haselbach, D.,Brown, N.G. (登録日: 2023-06-27, 公開日: 2023-09-27, 最終更新日: 2023-11-22)

主引用文献

Bodrug, T.,Welsh, K.A.,Bolhuis, D.L.,Paulаkonis, E.,Martinez-Chacin, R.C.,Liu, B.,Pinkin, N.,Bonacci, T.,Cui, L.,Xu, P.,Roscow, O.,Amann, S.J.,Grishkovskaya, I.,Emanuele, M.J.,Harrison, J.S.,Steimel, J.P.,Hahn, K.M.,Zhang, W.,Zhong, E.D.,Haselbach, D.,Brown, N.G.
Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C).
Nat.Struct.Mol.Biol., 30:1663-1674, 2023

PubMed Abstract: Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear. Here we present time-resolved cryogenic electron microscopy studies of the 1.2 MDa E3 ubiquitin ligase, known as the anaphase-promoting complex/cyclosome (APC/C), and its E2 co-enzymes (UBE2C/UBCH10 and UBE2S) during substrate polyubiquitination. Using cryoDRGN (Deep Reconstructing Generative Networks), a neural network-based approach, we reconstruct the conformational changes undergone by the human APC/C during polyubiquitination, directly visualize an active E3-E2 pair modifying its substrate, and identify unexpected interactions between multiple ubiquitins with parts of the APC/C machinery, including its coactivator CDH1. Together, we demonstrate how modification of substrates with nascent ubiquitin chains helps to potentiate processive substrate polyubiquitination, allowing us to model how a ubiquitin ligase builds a proteasomal degradation signal.

PubMed: 37735619
DOI: 10.1038/s41594-023-01105-5

実験手法

ELECTRON MICROSCOPY (4 Å)