Genome-wide analysis of eukaryotic twin CX9C proteins

Abstract

Twin CX₉C proteins are eukaryotic proteins that derive their name from their characteristic motif, consisting of two pairs of cysteines that form two disulfide bonds stabilizing a coiled coil–helix–coiled coil–helix (CHCH) fold. The best characterized of these proteins are Cox17, a copper chaperone acting in cytochrome c oxidase biogenesis, and Mia40, the central component of a system for protein import into the mitochondrial inter-membrane space (IMS). However, the range of possible functions for these proteins is unclear. Here, we performed a systematic search of twin CX₉C proteins in eukaryotic organisms, and classified them into groups of putative homologues, by combining bioinformatics methods with literature analysis. Our results suggest that the functions of most twin CX₉C proteins vary around the common theme of playing a scaffolding role, which can tie their observed roles in mitochondrial structure and function. This study will enhance the present annotation of eukaryotic proteomes, and will provide a rational basis for future experimental work aimed at a deeper understanding of this remarkable class of proteins.