6nl3
From Proteopedia
Solution structure of human Coa6
Structural highlights
DiseaseCOA6_HUMAN Fatal infantile cytochrome C oxidase deficiency. The disease is caused by mutations affecting the gene represented in this entry. FunctionCOA6_HUMAN Involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2. Thereby, may regulate early steps of complex IV assembly. Mitochondrial respiratory chain complex IV or cytochrome c oxidase is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. May also be required for efficient formation of respiratory supercomplexes comprised of complexes III and IV.[1] [2] [3] Publication Abstract from PubMedIn eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones and redox proteins including SCO1, SCO2, and COA6, a recently discovered protein whose molecular function is unknown. To uncover the molecular mechanism by which COA6 and SCO proteins mediate copper delivery to COX2, we have solved the solution structure of COA6, which reveals a coiled-coil-helix-coiled-coil-helix domain typical of redox-active proteins found in the mitochondrial inter-membrane space. Accordingly, we demonstrate that COA6 can reduce the copper-coordinating disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. Finally, our determination of the interaction surfaces and reduction potentials of COA6 and its client proteins provides a mechanism of how metallochaperone and disulfide reductase activities are coordinated to deliver copper to CcO. COA6 Is Structurally Tuned to Function as a Thiol-Disulfide Oxidoreductase in Copper Delivery to Mitochondrial Cytochrome c Oxidase.,Soma S, Morgada MN, Naik MT, Boulet A, Roesler AA, Dziuba N, Ghosh A, Yu Q, Lindahl PA, Ames JB, Leary SC, Vila AJ, Gohil VM Cell Rep. 2019 Dec 17;29(12):4114-4126.e5. doi: 10.1016/j.celrep.2019.11.054. PMID:31851937[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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