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-Structure paper
| タイトル | Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 7505, Year 2024 |
| 掲載日 | 2024年8月29日 |
著者 | Ian Cooney / Heidi L Schubert / Karina Cedeno / Olivia N Fisher / Richard Carson / John C Price / Christopher P Hill / Peter S Shen / ![]() |
| PubMed 要旨 | The Cdc48 AAA+ ATPase is an abundant and essential enzyme that unfolds substrates in multiple protein quality control pathways. The enzyme includes two conserved AAA+ ATPase motor domains, D1 and D2, ...The Cdc48 AAA+ ATPase is an abundant and essential enzyme that unfolds substrates in multiple protein quality control pathways. The enzyme includes two conserved AAA+ ATPase motor domains, D1 and D2, that assemble as hexameric rings with D1 stacked above D2. Here, we report an ensemble of native structures of Cdc48 affinity purified from budding yeast lysate in complex with the adaptor Shp1 in the act of unfolding substrate. Our analysis reveals a continuum of structural snapshots that spans the entire translocation cycle. These data uncover elements of Shp1-Cdc48 interactions and support a 'hand-over-hand' mechanism in which the sequential movement of individual subunits is closely coordinated. D1 hydrolyzes ATP and disengages from substrate prior to D2, while D2 rebinds ATP and re-engages with substrate prior to D1, thereby explaining the dominant role played by the D2 motor in substrate translocation/unfolding. |
リンク | Nat Commun / PubMed:39209885 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.9 - 4.3 Å |
| 構造データ | EMDB-41992, PDB-8u7t: EMDB-42025, PDB-8u8i: EMDB-42032, PDB-8u9c: EMDB-42038, PDB-8u9p: EMDB-42039, PDB-8u9q: EMDB-42042, PDB-8u9z: EMDB-42043, PDB-8ua0: EMDB-42047, PDB-8ua1: EMDB-42057, PDB-8uaa: EMDB-42076, PDB-8ub4: |
| 化合物 | ![]() ChemComp-08T: ![]() ChemComp-MG: ![]() ChemComp-ADP: |
| 由来 |
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キーワード | CHAPERONE / unfoldase / AAA ATPase / p97 / Cdc48 |
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