9B59

Ubiquitin E2-Ub-E3 HECT tetrahedral transthiolation intermediate mimic - state 5

これはPDB形式変換不可エントリーです。

9B59 の概要

• エントリーDOI: 10.2210/pdb9b59/pdb
• 関連するPDBエントリー: 9B55 9B56 9B57 9B58 9B5A 9B5B
• EMDBエントリー: 44204
• 分子名称: Ubiquitin-conjugating enzyme E2 4, Ubiquitin, E3 ubiquitin-protein ligase pub2, ... (4 entities in total)
• 機能のキーワード: ubiquitin, e2, e3, hect, nedd4, rsp5, pub2, ubc4, transthioesterification, thioester, transthiolation, tetrahedral intermediate, adenylation, inhibitor, ligase, nucleus, phosphoprotein, ubl conjugation pathway, ubl, atp atp-binding, amp, nucleotide-binding, isopeptide bond
• 由来する生物種: Schizosaccharomyces pombe 972h-; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70129.23

構造登録者

Kochanczyk, T.,Lima, C.D. (登録日: 2024-03-22, 公開日: 2024-06-05, 最終更新日: 2024-09-18)

主引用文献

Kochanczyk, T.,Hann, Z.S.,Lux, M.C.,Delos Reyes, A.M.V.,Ji, C.,Tan, D.S.,Lima, C.D.
Structural basis for transthiolation intermediates in the ubiquitin pathway.
Nature, 633:216-223, 2024

PubMed Abstract: Transthiolation (also known as transthioesterification) reactions are used in the biosynthesis of acetyl coenzyme A, fatty acids and polyketides, and for post-translational modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins. For the Ub pathway, E1 enzymes catalyse transthiolation from an E1~Ub thioester to an E2~Ub thioester. Transthiolation is also required for transfer of Ub from an E2~Ub thioester to HECT (homologous to E6AP C terminus) and RBR (ring-between-ring) E3 ligases to form E3~Ub thioesters. How isoenergetic transfer of thioester bonds is driven forward by enzymes in the Ub pathway remains unclear. Here we isolate mimics of transient transthiolation intermediates for E1-Ub(T)-E2 and E2-Ub(T)-E3 complexes (where T denotes Ub in a thioester or Ub undergoing transthiolation) using a chemical strategy with native enzymes and near-native Ub to capture and visualize a continuum of structures determined by single-particle cryo-electron microscopy. These structures and accompanying biochemical experiments illuminate conformational changes in Ub, E1, E2 and E3 that are coordinated with the chemical reactions to facilitate directional transfer of Ub from each enzyme to the next.

PubMed: 39143218
DOI: 10.1038/s41586-024-07828-9

実験手法

ELECTRON MICROSCOPY (3.49 Å)