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

ABSTRACT: 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 W59CCoa6-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 W59CCoa6 protein provides a structural explanation for the loss-of-function mutation.

SUBMITTER: Maghool S

PROVIDER: S-EPMC6743065 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Maghool Shadi S Cooray N Dinesha G NDG Stroud David A DA Aragão David D Ryan Michael T MT Maher Megan J MJ

Life science alliance 20190912 5

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 W59CCoa ...[more]

PMID: 31515291

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