Mitochondrial COA7 is a heme-binding protein with disulfide reductase activity, which acts in the early stages of complex IV assembly

Abstract

Significance Assembly factors play key roles in the biogenesis of mitochondrial protein complexes, regulating their stabilities, activities, and incorporation of essential cofactors. Cytochrome c oxidase assembly factor 7 (COA7) is a metazoan-specific assembly factor, the absence or mutation of which in humans accompanies complex IV assembly defects and neurological conditions. Here, we report the crystal structure of COA7 to 2.4 Å resolution, revealing a banana-shaped molecule composed of five helix-turn-helix (α/α) repeats. COA7 binds heme with micromolar affinity, even though the protein structure does not resemble previously characterized heme-binding proteins. The heme-bound COA7 can redox cycle between oxidation states Fe(II) and Fe(III) and shows disulfide reductase activity toward copper binding assembly factors. We propose that COA7 functions to facilitate the biogenesis of the binuclear copper site (Cu A ) of complex IV.