| Structural highlights
Disease
[COA6_HUMAN] Fatal infantile cytochrome C oxidase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
[COA6_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 PubMed
Assembly factors play key roles in the biogenesis of many multi-subunit protein complexes regulating their stability, activity, and the incorporation of essential cofactors. The human assembly factor Coa6 participates in the biogenesis of the CuA site in complex IV (cytochrome c oxidase, COX). Patients with mutations in Coa6 suffer from mitochondrial disease due to complex IV deficiency. Here, we present the crystal structures of human Coa6 and the pathogenic (W59C)Coa6-mutant protein. These structures show that Coa6 has a 3-helical bundle structure, with the first 2 helices tethered by disulfide bonds, one of which likely provides the copper-binding site. Disulfide-mediated oligomerization of the (W59C)Coa6 protein provides a structural explanation for the loss-of-function mutation.
Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6.,Maghool S, Cooray NDG, Stroud DA, Aragao D, Ryan MT, Maher MJ Life Sci Alliance. 2019 Sep 12;2(5). pii: 2/5/e201900458. doi:, 10.26508/lsa.201900458. Print 2019 Oct. PMID:31515291[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghosh A, Trivedi PP, Timbalia SA, Griffin AT, Rahn JJ, Chan SS, Gohil VM. Copper supplementation restores cytochrome c oxidase assembly defect in a mitochondrial disease model of COA6 deficiency. Hum Mol Genet. 2014 Jul 1;23(13):3596-606. doi: 10.1093/hmg/ddu069. Epub 2014 Feb, 18. PMID:24549041 doi:http://dx.doi.org/10.1093/hmg/ddu069
- ↑ Pacheu-Grau D, Bareth B, Dudek J, Juris L, Vogtle FN, Wissel M, Leary SC, Dennerlein S, Rehling P, Deckers M. Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies. Cell Metab. 2015 Jun 2;21(6):823-33. doi: 10.1016/j.cmet.2015.04.012. Epub 2015, May 7. PMID:25959673 doi:http://dx.doi.org/10.1016/j.cmet.2015.04.012
- ↑ Stroud DA, Maher MJ, Lindau C, Vogtle FN, Frazier AE, Surgenor E, Mountford H, Singh AP, Bonas M, Oeljeklaus S, Warscheid B, Meisinger C, Thorburn DR, Ryan MT. COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2. Hum Mol Genet. 2015 Oct 1;24(19):5404-15. doi: 10.1093/hmg/ddv265. Epub 2015 Jul , 9. PMID:26160915 doi:http://dx.doi.org/10.1093/hmg/ddv265
- ↑ Maghool S, Cooray NDG, Stroud DA, Aragao D, Ryan MT, Maher MJ. Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6. Life Sci Alliance. 2019 Sep 12;2(5). pii: 2/5/e201900458. doi:, 10.26508/lsa.201900458. Print 2019 Oct. PMID:31515291 doi:http://dx.doi.org/10.26508/lsa.201900458
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