Abstract
Cytochrome c oxidase (CcO) is the terminal enzyme of our respiratory chains. It is a large membrane protein (200kDa) composed of 13 subunits. Three are encoded by the mitochondrial DNA and form the catalytic core but the function of the ten other subunits, which are nuclear DNA encoded and unique to mitochondrial forms of the enzyme, remains unknown. Of particular interest are evidences for roles in supercomplex formation and allosteric regulation of CcO’s core catalytic activity. We will address these key questions by solving at high-resolution the structure of the only mitochondrial enzyme that permits mutagenesis to test functional hypothesis.
References
- Rich PR and Maréchal A (2012) Electron transfer chains: structures, mechanisms and energy coupling, Comprehensive Biophysics 8, 72-93
- Letts JA, Fiedorczuk K, Sazanov LA (2016) The architecture of respiratory supercomplexes, Nature 537 (7322), 644-48
- Mileykovskaya E et al (2012) Arrangement of the respiratory chain complexes in Saccharomyces cerevisiae supercomplex III2IV2 revealed by single particle cryo-electron microscopy, J Biol Chem 287, 23095-103
- Rydström Lundin C et al (2016) Regulatory role of the respiratory supercomplex factors in Saccharomyces cerevisiae, PNAS 113 (31), E4476-85
- Milenkovic D et al (2017) The enigma of the respiratory chain supercomplex, Cell Metab 25 (4), 765-76