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Docking and molecular simulations reveal a quinone‐binding site on the surface of respiratory complex I
Author(s) -
Djurabekova Amina,
Galemou Yoga Etienne,
Nyman Aino,
Pirttikoski Antti,
Zickermann Volker,
Haapanen Outi,
Sharma Vivek
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14346
Subject(s) - docking (animal) , yarrowia , molecular dynamics , chemistry , binding site , protein subunit , biophysics , stereochemistry , electron transport chain , quinone , electron transport complex i , respiratory chain , crystallography , computational chemistry , biochemistry , biology , mitochondrion , medicine , nursing , gene
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.