High-resolution structure and dynamics of mitochondrial complex I—Insights into the proton pumping mechanism
Kristian Parey, Jonathan Lasham, Deryck J. Mills, Amina Djurabekova, Outi Haapanen, Etienne Galemou Yoga, Hao Xie, Werner Kühlbrandt, Vivek Sharma, Janet Vonck, Volker Zickermann
Abstract
at 2.1-Å resolution, which reveals the positions of more than 1600 protein-bound water molecules, of which ~100 are located in putative proton translocation pathways. Another structure of the same complex under steady-state activity conditions at 3.4-Å resolution indicates conformational transitions that we associate with proton injection into the central hydrophilic axis. By combining high-resolution structural data with site-directed mutagenesis and large-scale molecular dynamic simulations, we define details of the proton translocation pathways and offer insights into the redox-coupled proton pumping mechanism of complex I.