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-Structure paper
タイトル | Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 2393, Year 2019 |
掲載日 | 2019年6月3日 |
著者 | Alexandrea N Rizo / JiaBei Lin / Stephanie N Gates / Eric Tse / Stephen M Bart / Laura M Castellano / Frank DiMaio / James Shorter / Daniel R Southworth / |
PubMed 要旨 | Bacterial ClpB and yeast Hsp104 are homologous Hsp100 protein disaggregases that serve critical functions in proteostasis by solubilizing protein aggregates. Two AAA+ nucleotide binding domains (NBDs) ...Bacterial ClpB and yeast Hsp104 are homologous Hsp100 protein disaggregases that serve critical functions in proteostasis by solubilizing protein aggregates. Two AAA+ nucleotide binding domains (NBDs) power polypeptide translocation through a central channel comprised of a hexameric spiral of protomers that contact substrate via conserved pore-loop interactions. Here we report cryo-EM structures of a hyperactive ClpB variant bound to the model substrate, casein in the presence of slowly hydrolysable ATPγS, which reveal the translocation mechanism. Distinct substrate-gripping interactions are identified for NBD1 and NBD2 pore loops. A trimer of N-terminal domains define a channel entrance that binds the polypeptide substrate adjacent to the topmost NBD1 contact. NBD conformations at the seam interface reveal how ATP hydrolysis-driven substrate disengagement and re-binding are precisely tuned to drive a directional, stepwise translocation cycle. |
リンク | Nat Commun / PubMed:31160557 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 4.1 Å |
構造データ | EMDB-20004: CryoEM map of the hyperactive ClpB mutant K476C, bound to casein, pre-state EMDB-20005: CryoEM map of the hyperactive ClpB mutant K476C, bound to casein, post-state EMDB-20049: CryoEM focus classification map of the hyperactive ClpB mutant K476C, bound to casein, pre-state EMDB-20050: CryoEM focus classification map of the hyperactive ClpB mutant K476C, bound to casein, post-state EMDB-20051: CryoEM focus classification map of the hyperactive ClpB mutant K476C, bound to casein, NTD-trimer |
化合物 | ChemComp-AGS: ChemComp-ADP: |
由来 |
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キーワード | CHAPERONE / disaggregase / CLPB / AAA+ |