7MQZ

Cytochrome c oxidase assembly factor 7

Summary for 7MQZ

• Entry DOI: 10.2210/pdb7mqz/pdb
• Descriptor: Cytochrome c oxidase assembly factor 7 (2 entities in total)
• Functional Keywords: mitochondria, complex iv assembly factor, electron transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 26155.59

Authors

Maghool, S.,Maher, M.J. (deposition date: 2021-05-07, release date: 2022-03-16, Last modification date: 2023-10-18)

Primary citation

Formosa, L.E.,Maghool, S.,Sharpe, A.J.,Reljic, B.,Muellner-Wong, L.,Stroud, D.A.,Ryan, M.T.,Maher, M.J.
Mitochondrial COA7 is a heme-binding protein with disulfide reductase activity, which acts in the early stages of complex IV assembly.
Proc.Natl.Acad.Sci.USA, 119:-, 2022

PubMed Abstract: Cytochrome oxidase (COX) assembly factor 7 (COA7) is a metazoan-specific assembly factor, critical for the biogenesis of mitochondrial complex IV (cytochrome oxidase). Although mutations in COA7 have been linked to complex IV assembly defects and neurological conditions such as peripheral neuropathy, ataxia, and leukoencephalopathy, the precise role COA7 plays in the biogenesis of complex IV is not known. Here, we show that loss of COA7 blocks complex IV assembly after the initial step where the COX1 module is built, progression from which requires the incorporation of copper and addition of the COX2 and COX3 modules. The crystal structure of COA7, determined to 2.4 Å resolution, reveals a banana-shaped molecule composed of five helix-turn-helix (α/α) repeats, tethered by disulfide bonds. COA7 interacts transiently with the copper metallochaperones SCO1 and SCO2 and catalyzes the reduction of disulfide bonds within these proteins, which are crucial for copper relay to COX2. COA7 binds heme with micromolar affinity, through axial ligation to the central iron atom by histidine and methionine residues. We therefore propose that COA7 is a heme-binding disulfide reductase for regenerating the copper relay system that underpins complex IV assembly.

PubMed: 35210360
DOI: 10.1073/pnas.2110357119

Experimental method

X-RAY DIFFRACTION (2.39 Å)