1. Assessment of amino acid charge states based on cryo-electron microscopy and molecular dynamics simulations of respiratory complex I.
- Author
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Lasham J, Djurabekova A, Kolypetris G, Zickermann V, Vonck J, and Sharma V
- Subjects
- Amino Acids chemistry, Fungal Proteins chemistry, Fungal Proteins metabolism, Protein Conformation, Molecular Dynamics Simulation, Electron Transport Complex I chemistry, Electron Transport Complex I metabolism, Cryoelectron Microscopy methods, Yarrowia enzymology
- Abstract
The charge states of titratable amino acid residues play a key role in the function of membrane-bound bioenergetic proteins. However, determination of these charge states both through experimental and computational approaches is extremely challenging. Cryo-EM density maps can provide insights on the charge states of titratable amino acid residues. By performing classical atomistic molecular dynamics simulations on the high resolution cryo-EM structures of respiratory complex I from Yarrowia lipolytica, we analyze the conformational and charge states of a key acidic residue in its ND1 subunit, aspartic acid D203, which is also a mitochondrial disease mutation locus. We suggest that in the native state of respiratory complex I, D203 is negatively charged and maintains a stable hydrogen bond to a conserved arginine residue. Alternatively, upon conformational change in the turnover state of the enzyme, its sidechain attains a charge-neutral status. We discuss the implications of this analysis on the molecular mechanism of respiratory complex I., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2025
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