Structure and functionality of a multimeric human COQ7:COQ9 complex.
In: Molecular cell, vol. 82, no. 22, pp. 4307-4323.e10, 2022
Online
academicJournal
Zugriff:
Coenzyme Q (CoQ) is a redox-active lipid essential for core metabolic pathways and antioxidant defense. CoQ is synthesized upon the mitochondrial inner membrane by an ill-defined "complex Q" metabolon. Here, we present structure-function analyses of a lipid-, substrate-, and NADH-bound complex comprising two complex Q subunits: the hydroxylase COQ7 and the lipid-binding protein COQ9. We reveal that COQ7 adopts a ferritin-like fold with a hydrophobic channel whose substrate-binding capacity is enhanced by COQ9. Using molecular dynamics, we further show that two COQ7:COQ9 heterodimers form a curved tetramer that deforms the membrane, potentially opening a pathway for the CoQ intermediates to translocate from the bilayer to the proteins' lipid-binding sites. Two such tetramers assemble into a soluble octamer with a pseudo-bilayer of lipids captured within. Together, these observations indicate that COQ7 and COQ9 cooperate to access hydrophobic precursors within the membrane and coordinate subsequent synthesis steps toward producing CoQ.
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Structure and functionality of a multimeric human COQ7:COQ9 complex.
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Autor/in / Beteiligte Person: | Manicki, M. ; Aydin, H. ; Abriata, L.A. ; Overmyer, K.A. ; Guerra, R.M. ; Coon, J.J. ; Dal Peraro, M. ; Frost, A. ; Pagliarini, D.J. |
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Zeitschrift: | Molecular cell, vol. 82, no. 22, pp. 4307-4323.e10, 2022 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 1097-2765 (print) |
DOI: | 10.1016/j.molcel.2022.10.003 |
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