RT Journal Article
SR Electronic
T1 Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900458
DO 10.26508/lsa.201900458
VO 2
IS 5
A1 Shadi Maghool
A1 N Dinesha G Cooray
A1 David A Stroud
A1 David Aragão
A1 Michael T Ryan
A1 Megan J Maher
YR 2019
UL https://www.life-science-alliance.org/content/2/5/e201900458.abstract
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.