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

Shadi Maghool, N. Dinesha G. Cooray, David A Stroud, David Aragão, Michael T Ryan, Megan J Maher

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Article numbere201900458
Number of pages12
JournalLife Science Alliance
Volume2
Issue number5
DOIs
Publication statusPublished - Oct 2019

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