Structural insights into electron transfer in caa3-type cytochrome oxidase

• Published in: Nature (London) 2012-07, Vol.487 (7408), p.514-518
• Main Authors: Lyons, Joseph A., Aragão, David, Slattery, Orla, Pisliakov, Andrei V., Soulimane, Tewfik, Caffrey, Martin
• Format: Article
• Language: English
• Subjects: 631/45/535; 631/57/2272; Analytical, structural and metabolic biochemistry; Azurin - metabolism; Biological and medical sciences; Catalytic Domain; Cell Membrane - metabolism; Crystallization; Crystallography, X-Ray; Cytochrome c Group - metabolism; Cytochromes a - metabolism; Cytochromes a3 - metabolism; Electron Transport; Electron Transport Complex IV - chemistry; Electron Transport Complex IV - metabolism; Electrons; Fundamental and applied biological sciences. Psychology; Glycerophospholipids - chemistry; Glycerophospholipids - metabolism; Humanities and Social Sciences; letter; Models, Molecular; Molecular and cellular biology; multidisciplinary; Oxygen - metabolism; Protein Structure, Tertiary; Protein Subunits - chemistry; Protein Subunits - metabolism; Protons; Science; Science (multidisciplinary); Thermus thermophilus - enzymology; Water - chemistry; Water - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11182

The caa 3 -type cytochrome oxidase structure described here provides insight into the coupling of energy transduction to the complete reduction of oxygen. Electron transfer in a cyctochrome c oxidase The X-ray crystal structure of the cytochrome c oxidase caa 3 from Thermus thermophilus has been determined at 2.36-ångström resolution. Cytochrome c oxidase is a multisubunit integral membrane protein that functions as the terminal enzyme in the respiratory chain of mitochondria and aerobic prokaryotes. The caa 3 -type oxidase is covalently tethered to a cytochrome c domain, which is responsible for transferring electrons to the oxidase domain. The structure provides a framework for examining how this integral membrane complex couples energy transduction to the complete reduction of oxygen. Cytochrome c oxidase is a member of the haem copper oxidase superfamily (HCO) 1 . HCOs function as the terminal enzymes in the respiratory chain of mitochondria and aerobic prokaryotes, coupling molecular oxygen reduction to transmembrane proton pumping. Integral to the enzyme’s function is the transfer of electrons from cytochrome c to the oxidase via a transient association of the two proteins. Electron entry and exit are proposed to occur from the same site on cytochrome c 2 , 3 , 4 . Here we report the crystal structure of the caa 3 -type cytochrome oxidase from Thermus thermophilus , which has a covalently tethered cytochrome c domain. Crystals were grown in a bicontinuous mesophase using a synthetic short-chain monoacylglycerol as the hosting lipid. From the electron density map, at 2.36 Å resolution, a novel integral membrane subunit and a native glycoglycerophospholipid embedded in the complex were identified. Contrary to previous electron transfer mechanisms observed for soluble cytochrome c , the structure reveals the architecture of the electron transfer complex for the fused cupredoxin/cytochrome c domain, which implicates different sites on cytochrome c for electron entry and exit. Support for an alternative to the classical proton gate characteristic of this HCO class is presented.