atomistic insights into the structure of a key bioenergetic protein - atomistic insights into the structure of a key bioenergetic protein - @CSC
Experiments and simulations provide atomistic insights into the structure of a key bioenergetic protein
Cellular respiration is a process by which cells convert biochemical energy from nutrients for their use. In the mitochondrion, power house of the cell, electron transport chain or respiratory chain drives the synthesis of ATP – biological energy currency.
Researchers from Finland and Germany have investigated experimentally and computationally the structure of a key enzyme, the respiratory complex I, and found an important substrate molecule bound to the protein cavity.
Respiratory complex I performs the subtle electron and proton transfer reactions and significantly contributes to biological energy generation in mitochondria.
Computing with CSC and PRACE resources
By applying state-of-the-art cryo electron microscopy techniques, researchers from Max Planck Institute of Biophysics and Goethe University, Frankfurt solved the structure of complex I from Yarrowia lipolytica at a resolution of 3.2 Å (1 ångström = 10–10 m = 0.1 nm).
Researchers from University of Helsinki studied this structure with high resolution atomistic molecular dynamics simulations. The model system was massive, consisting of ~1.3 million atoms and was simulated for microseconds.
Remarkably, a substrate molecule (called ubiquinone that accepts or donates electrons in mitochondria) is observed in this new structure at a site, which was earlier predicted based on molecular dynamics simulations.
– The results from computer simulations complemented the structural and biochemical data leading to a better understanding of biological energy conversion, said researcher Outi Haapanen at University of Helsinki.
The study used CSC's Grand Challenge resources and the resources of the Barcelona Supercomputing Center through the PRACE network.
– Our joint efforts, combining structural biology with molecular simulation approaches, once again shows the importance of cross-disciplinary approaches in solving difficult biological questions. Moreover, the finding of a quinone molecule at the site predicted by our computer simulations earlier, very much strengthens the central role simulations play in studies of enzyme catalysis, said Vivek Sharma, who led the simulation project at the Department of Physics, University of Helsinki.
Press release, University of Helsinki, High resolution structure and molecular simulations of a key bioenergetic protein
Kristian Parey, Outi Haapanen, Vivek Sharma, Harald Köfeler, Thomas Züllig, Simone Prinz, Karin Siegmund, Ilka Wittig, Deryck J. Mills, Janet Vonck, Werner Kühlbrandt and Volker Zickermann. High-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease. Science Advances 11 Dec 2019.
Redox-coupled quinone dynamics in the respiratory complex I. PNAS Sep 2018.
Role of Second Quinone Binding Site in Proton Pumping by Respiratory Complex I. Front. Chem. Apr 2019.