Journal article
Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6
Shadi Maghool, N Dinesha G Cooray, David A Stroud, David Aragao, Michael T Ryan, Megan J Maher
LIFE SCIENCE ALLIANCE | LIFE SCIENCE ALLIANCE LLC | Published : 2019
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..
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Awarded by Australian Research Council
Awarded by National Health and Medical Research Council
Funding Acknowledgements
This study was funded by the Australian Research Council (DP140102746 to MJ Maher), the National Health and Medical Research Council (GNT1165217 to MT Ryan and MJ Maher; GNT1140851 to DA Stroud), and an Australian Government Research Training Program Scholarship to S Maghool. Aspects of this research were undertaken on the Macromolecular Crystallography beamline MX2 at the Australian Synchrotron (Victoria, Australia) and we thank the beamline staff for their enthusiastic and professional support. We also acknowledge the La Trobe University Comprehensive Proteomics Platform for providing infrastructure for this study.