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

Life Sci Alliance. 2019 Sep 12;2(5):e201900458. doi: 10.26508/lsa.201900458. Print 2019 Oct.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Copper / metabolism*
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Loss of Function Mutation
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • COA6 protein, human
  • Carrier Proteins
  • Mitochondrial Proteins
  • Copper

Associated data

  • PDB/6PCE
  • PDB/6PCF
  • PDB/2RNB
  • PDB/2EIJ
  • PDB/2K3J
  • PDB/1HP8
  • PDB/2LQL
  • PDB/2LQT
  • PDB/2ZXW
  • PDB/2GVP
  • PDB/2RLI
  • PDB/5Z62