1. Docking and molecular simulations reveal a quinone-binding site on the surface of respiratory complex I
- Author
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Amina Djurabekova, Etienne Galemou Yoga, Aino Nyman, Antti Pirttikoski, Volker Zickermann, Outi Haapanen, Vivek Sharma, Materials Physics, Department of Physics, and Institute of Biotechnology
- Subjects
49-KDA SUBUNIT ,STRUCTURAL DYNAMICS ,Biophysics ,mitochondrial respiratory chain ,Yarrowia ,bioenergetics ,Biochemistry ,114 Physical sciences ,Protein Domains ,Structural Biology ,Genetics ,ACID-RESIDUES ,CRYSTAL-STRUCTURE ,molecular ,Molecular Biology ,PROTON PUMP ,Binding Sites ,Electron Transport Complex I ,complex I ,Quinones ,Cell Biology ,dynamics simulations ,NADH ,FORCE-FIELD ,MEMBRANE ,COUPLING MECHANISM ,UBIQUINONE REACTION SITE - Abstract
The first component of the mitochondrial electron transport chain is respiratory complex I. Several high-resolution structures of complex I from different species have been resolved. However, despite these significant achievements, the mechanism of redox-coupled proton pumping remains elusive. Here, we combined atomistic docking, molecular dynamics simulations, and site-directed mutagenesis on respiratory complex I from Yarrowia lipolytica to identify a quinone (Q)-binding site on its surface near the horizontal amphipathic helices of ND1 and NDUFS7 subunits. The surface-bound Q makes stable interactions with conserved charged and polar residues, including the highly conserved Arg72 from the NDUFS7 subunit. The binding and dynamics of a Q molecule at the surface-binding site raise interesting possibilities about the mechanism of complex I, which are discussed.
- Published
- 2022