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-Structure paper
タイトル | Structures of Respiratory Supercomplex I+III Reveal Functional and Conformational Crosstalk. |
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ジャーナル・号・ページ | Mol Cell, Vol. 75, Issue 6, Page 1131-11146.e6, Year 2019 |
掲載日 | 2019年9月19日 |
著者 | James A Letts / Karol Fiedorczuk / Gianluca Degliesposti / Mark Skehel / Leonid A Sazanov / |
PubMed 要旨 | The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We ...The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII, suggesting that interaction with CI disrupts CIII symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs. |
リンク | Mol Cell / PubMed:31492636 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 - 7.5 Å |
構造データ | EMDB-4479, PDB-6q9b: EMDB-4480, PDB-6q9d: EMDB-4481, PDB-6q9e: EMDB-4482, PDB-6qa9: EMDB-4506: EMDB-4507: |
化合物 | ChemComp-3PE: ChemComp-CDL: ChemComp-PC1: ChemComp-ZMP: ChemComp-SF4: ChemComp-FMN: ChemComp-FES: ChemComp-ZN: ChemComp-NDP: ChemComp-HEM: ChemComp-HEC: |
由来 |
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キーワード | ELECTRON TRANSPORT / complex I / membrane arm / cellular respiration / mitochondria / peripheral arm / complex III / supercomplex |