12 Nov 2021 - Structure of respiratory complex I resolved at 2.1 Å resolution
All life processes require a constant supply of energy. To meet this demand, ATP serves as the cell's molecular fuel. The driving force for ATP synthesis is the so-called mitochondrial respiratory chain, with mitochondrial complex I forming the starting point. Mitochondrial complex I is a very large membrane protein complex, but despite its central role in aerobic energy metabolism, its molecular mechanism is still largely unknown. In a study published today in Science Advances, the Zickermann group together with colleagues from the MPI of Biophysics and the University of Helsinki now provides groundbreaking new insights into this key player of biological energy conversion.
Using cryo-electron microscopy, they were able to determine the molecular structure of complex I with unprecedented resolution. Proton transfer reactions along chains of water molecules and certain amino acid side chains play a central role in the function of complex I. The excellent quality of the structural data made it possible to precisely localize water molecules in the protein structure and to draw important conclusions about proton transfer pathways. The high-resolution structural data were used for extensive computer simulations to capture the dynamics of the structure. The results provide a new and detailed picture of how a molecular machine works.