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-Structure paper
タイトル | Structural basis for transthiolation intermediates in the ubiquitin pathway. |
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ジャーナル・号・ページ | Nature, Vol. 633, Issue 8028, Page 216-223, Year 2024 |
掲載日 | 2024年8月14日 |
著者 | Tomasz Kochańczyk / Zachary S Hann / Michaelyn C Lux / Avelyn Mae V Delos Reyes / Cheng Ji / Derek S Tan / Christopher D Lima / |
PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:39143218 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.5 - 4.16 Å |
構造データ | EMDB-44200, PDB-9b55: EMDB-44201, PDB-9b56: EMDB-44202, PDB-9b57: EMDB-44203, PDB-9b58: EMDB-44204, PDB-9b59: EMDB-44205, PDB-9b5a: EMDB-44206, PDB-9b5b: EMDB-44207, PDB-9b5c: EMDB-44208, PDB-9b5d: EMDB-44209, PDB-9b5e: EMDB-44210, PDB-9b5f: EMDB-44211, PDB-9b5g: EMDB-44212, PDB-9b5h: EMDB-44213, PDB-9b5i: EMDB-44214, PDB-9b5j: EMDB-44215, PDB-9b5k: EMDB-44216, PDB-9b5l: EMDB-44217, PDB-9b5m: EMDB-44218, PDB-9b5n: EMDB-44219, PDB-9b5o: EMDB-44220, PDB-9b5p: EMDB-44221, PDB-9b5q: EMDB-44222, PDB-9b5r: EMDB-44223, PDB-9b5s: EMDB-44224, PDB-9b5t: EMDB-44225, PDB-9b5u: EMDB-44226, PDB-9b5v: EMDB-44227, PDB-9b5w: EMDB-44228, PDB-9b5x: |
化合物 | PDB-1aiv: ChemComp-MG: ChemComp-ATP: ChemComp-POP: ChemComp-AMP: |
由来 |
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キーワード | LIGASE / UBIQUITIN / E2 / E3 / HECT / NEDD4 / RSP5 / PUB2 / UBC4 / TRANSTHIOESTERIFICATION / THIOESTER / TRANSTHIOLATION / TETRAHEDRAL INTERMEDIATE / ADENYLATION / INHIBITOR / NUCLEUS / PHOSPHOPROTEIN / UBL CONJUGATION PATHWAY / UBL / ATP ATP-BINDING / AMP / NUCLEOTIDE-BINDING / ISOPEPTIDE BOND / E1 / UBA1 / ATP / ATP-binding |