Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk

article Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk published yes James A Letts author 322DA418-F248-11E8-B48F-1D18A9856A870000-0002-9864-3586 Karol Fiedorczuk author 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0 Gianluca Degliesposti author Mark Skehel author Leonid A Sazanov author 338D39FE-F248-11E8-B48F-1D18A9856A870000-0002-0977-7989 LeSa department Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes project 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+III2 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 CIII2. 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 CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs. https://research-explorer.ista.ac.at/download/7395/7447/2019_MolecularCell_Letts.pdf application/pdfno Cell Press2019 eng Molecular Cell 1097-2765 31492636 00048661420000610.1016/j.molcel.2019.07.022 7561131-1146.e6 Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. 2019. Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Molecular Cell. 75(6), 1131–1146.e6. J.A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, L.A. Sazanov, Molecular Cell 75 (2019) 1131–1146.e6. Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Molecular Cell. 2019;75(6):1131-1146.e6. doi:<a href="https://doi.org/10.1016/j.molcel.2019.07.022">10.1016/j.molcel.2019.07.022</a> Letts, James A, Karol Fiedorczuk, Gianluca Degliesposti, Mark Skehel, and Leonid A Sazanov. “Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.” Molecular Cell. Cell Press, 2019. <a href="https://doi.org/10.1016/j.molcel.2019.07.022">https://doi.org/10.1016/j.molcel.2019.07.022</a>. Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M., & Sazanov, L. A. (2019). Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Molecular Cell. Cell Press. <a href="https://doi.org/10.1016/j.molcel.2019.07.022">https://doi.org/10.1016/j.molcel.2019.07.022</a> J. A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, and L. A. Sazanov, “Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk,” Molecular Cell, vol. 75, no. 6. Cell Press, p. 1131–1146.e6, 2019. Letts, James A., et al. “Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.” Molecular Cell, vol. 75, no. 6, Cell Press, 2019, p. 1131–1146.e6, doi:<a href="https://doi.org/10.1016/j.molcel.2019.07.022">10.1016/j.molcel.2019.07.022</a>. 73952020-01-29T16:02:33Z2024-10-22T09:34:12Z