Role of conformational change and lipidic ligands in function and regulation of Cytochrome c Oxidase

School Colloquium

As the consumer of 95% of the oxygen we breathe, cytochrome c oxidase plays a major role in the energy balance of the cell. Regulation of its oxygen reduction and proton pumping activity is therefore critical to physiological function in health and disease. The location and structure of pathways for protons that are required to support cytochrome c oxidase activity are still under debate, including their requirements for conserved residues and waters, and how they are gated to prevent or allow proton backflow. Recent high resolution crystal structures of bacterial and mammalian forms of oxidase reveal conserved positions of water and lipid, as well as a steroid binding site.  In addition, significant conformational changes have been resolved, linked to redox state. The findings provide new insights into potential regulatory ligands, proton transfer and gating mechanisms, as well as physiological implications.

Ferguson-Miller, Shelagh, Hiser, Carrie, Liu, Jian (2012) Gating and regulation of the cytochrome c oxidase proton pump. Biochimica et Biophysica Acta 1817: 489–494

Liu, Jian, Qin, Ling, S. Ferguson-Miller (2011) Role of Conformational Change and Conserved Water in the Cytochrome Oxidase Proton Pump: Crystallographic and On-Line Spectral Evidence. Proc.Natl.Acad.Sci. USA 108: 1284-1289

Buhrow, Leann, Ferguson-Miller, Shelagh, and Kuhn, Leslie A. (2012) “From Static Structure to Living Protein: Computational Analysis of Cytochrome c Oxidase Main-chain Flexibility” Biophysical J. 102: 2158-2166

For more information contact Prof. Raquel Lieberman (404-385-3663).