1. NMR structural analysis of the yeast cytochrome c oxidase subunit Cox13 and its interaction with ATP
- Author
-
Peter Brzezinski, Pontus Pettersson, Hannah Dawitz, Lena Mäler, Markus L. Björck, Pia Ädelroth, and Shu Zhou
- Subjects
Magnetic Resonance Spectroscopy ,Saccharomyces cerevisiae Proteins ,Physiology ,QH301-705.5 ,Protein subunit ,Dimer ,Saccharomyces cerevisiae ,Plant Science ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Electron Transport Complex IV ,chemistry.chemical_compound ,Adenosine Triphosphate ,Structural Biology ,Animals ,Cytochrome c oxidase ,Biology (General) ,Ecology, Evolution, Behavior and Systematics ,chemistry.chemical_classification ,C-terminus ,Solution structure ,Cell Biology ,Protein superfamily ,biology.organism_classification ,Transmembrane protein ,NMR ,ATP ,Enzyme ,chemistry ,Membrane protein ,Biophysics ,biology.protein ,Cattle ,General Agricultural and Biological Sciences ,Research Article ,Developmental Biology ,Biotechnology - Abstract
Background Mitochondrial respiration is organized in a series of enzyme complexes in turn forming dynamic supercomplexes. In Saccharomyces cerevisiae (baker’s yeast), Cox13 (CoxVIa in mammals) is a conserved peripheral subunit of Complex IV (cytochrome c oxidase, CytcO), localized at the interface of dimeric bovine CytcO, which has been implicated in the regulation of the complex. Results Here, we report the solution NMR structure of Cox13, which forms a dimer in detergent micelles. Each Cox13 monomer has three short helices (SH), corresponding to disordered regions in X-ray or cryo-EM structures of homologous proteins. Dimer formation is mainly induced by hydrophobic interactions between the transmembrane (TM) helix of each monomer. Furthermore, an analysis of chemical shift changes upon addition of ATP revealed that ATP binds at a conserved region of the C terminus with considerable conformational flexibility. Conclusions Together with functional analysis of purified CytcO, we suggest that this ATP interaction is inhibitory of catalytic activity. Our results shed light on the structural flexibility of an important subunit of yeast CytcO and provide structure-based insight into how ATP could regulate mitochondrial respiration.
- Published
- 2021