Mutations in a conserved loop in the PSST subunit of respiratory complex I affect ubiquinone binding and dynamics
| Autor: | Outi Haapanen, Vivek Sharma, Volker Zickermann, Ilka Wittig, Etienne Galemou Yoga, Karin Siegmund |
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| Přispěvatelé: | Materials Physics, Department of Physics |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cellular respiration Protein Conformation Ubiquinone Protein subunit 116 Chemical sciences Biophysics Sequence Homology Yarrowia Mitochondrion Molecular Dynamics Simulation Biochemistry 114 Physical sciences Catalysis Fungal Proteins Electron transfer 03 medical and health sciences 0302 clinical medicine Quinone binding Oxidoreductase Proton pumping Redox-coupled proton pumping Inner membrane QUINONE BINDING CRYSTAL-STRUCTURE Amino Acid Sequence YARROWIA-LIPOLYTICA OXIDOREDUCTASE Inner mitochondrial membrane chemistry.chemical_classification Ubiquinone binding ARCHITECTURE Binding Sites Electron Transport Complex I PURIFICATION Quinone dynamics Chemistry MEMBRANE DOMAIN Cell Biology Cell respiration Protein Subunits 030104 developmental biology MOLECULAR-DYNAMICS Mutation ND1 Mutagenesis Site-Directed 030217 neurology & neurosurgery CHARMM |
| Popis: | Respiratory complex I catalyses the reduction of ubiquinone (Q) from NADH coupled to proton pumping across the inner membrane of mitochondria. The electrical charging of the inner mitochondrial membrane drives the synthesis of ATP, which is used to power biochemical reactions of the cell. The recent surge in structural data on complex I from bacteria and mitochondria have contributed to significant understanding of its molecular architecture. However, despite these accomplishments, the role of various subdomains in redox-coupled proton pumping remains entirely unclear. In this work, we have mutated conserved residues in the loop of the PSST subunit that faces the similar to 30 angstrom long unique Q-binding tunnel of respiratory complex I. The data show a drastic decrease in Q reductase activity upon mutating several residues despite full assembly of the complex. In-silico modeling and multiple microsecond long molecular dynamics simulations of wild-type and enzyme variants with exchanges of conserved arginine residues revealed remarkable ejection of the bound Q from the site near terminal electron donor N2. Based on experiments and long-time scale molecular simulations, we identify microscopic elements that dynamically control the diffusion of Q and are central to redox-coupled proton pumping in respiratory complex I. |
| Databáze: | OpenAIRE |
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