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-Structure paper
Title | Structures of Respiratory Supercomplex I+III Reveal Functional and Conformational Crosstalk. |
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Journal, issue, pages | Mol Cell, Vol. 75, Issue 6, Page 1131-11146.e6, Year 2019 |
Publish date | Sep 19, 2019 |
Authors | James A Letts / Karol Fiedorczuk / Gianluca Degliesposti / Mark Skehel / Leonid A Sazanov / |
PubMed Abstract | 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. |
External links | Mol Cell / PubMed:31492636 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.8 - 7.5 Å |
Structure data | EMDB-4479, PDB-6q9b: EMDB-4480, PDB-6q9d: EMDB-4481, PDB-6q9e: EMDB-4482, PDB-6qa9: EMDB-4493, PDB-6qbx: EMDB-4494, PDB-6qc2: EMDB-4495, PDB-6qc3: EMDB-4496, PDB-6qc4: EMDB-4497, PDB-6qc5: EMDB-4498, PDB-6qc6: EMDB-4499, PDB-6qc7: EMDB-4500, PDB-6qc8: EMDB-4501, PDB-6qc9: EMDB-4502, PDB-6qca: EMDB-4505, PDB-6qcf: EMDB-4506: EMDB-4507: |
Chemicals | ChemComp-3PE: ChemComp-CDL: ChemComp-PC1: ChemComp-ZMP: ChemComp-SF4: ChemComp-FMN: ChemComp-FES: ChemComp-ZN: ChemComp-NDP: ChemComp-HEM: ChemComp-U10: ChemComp-HEC: |
Source |
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Keywords | ELECTRON TRANSPORT / complex I / membrane arm / cellular respiration / mitochondria / peripheral arm / complex III / supercomplex |