PT  - JOURNAL ARTICLE
AU  - Shadi Maghool
AU  - N Dinesha G Cooray
AU  - David A Stroud
AU  - David Aragão
AU  - Michael T Ryan
AU  - Megan J Maher
TI  - Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6
AID  - 10.26508/lsa.201900458
DP  - 2019 Oct 01
TA  - Life Science Alliance
PG  - e201900458
VI  - 2
IP  - 5
4099  - https://www.life-science-alliance.org/content/2/5/e201900458.short
4100  - https://www.life-science-alliance.org/content/2/5/e201900458.full
SO  - Life Sci. Alliance2019 Oct 01; 2
AB  - 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.