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Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6

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 Cu(A) site in complex IV (cytochrome c oxidase, COX). Pat...

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Detalles Bibliográficos
Autores principales: Maghool, Shadi, Cooray, N Dinesha G, Stroud, David A, Aragão, David, Ryan, Michael T, Maher, Megan J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743065/
https://www.ncbi.nlm.nih.gov/pubmed/31515291
http://dx.doi.org/10.26508/lsa.201900458
Descripción
Sumario: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 Cu(A) 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.