The impacts of the mitochondrial myopathy-associated G58R mutation on the dynamic structural properties of CHCHD10

Abstract

The mitochondria are responsible for producing energy within the cell, and in mitochondrial myop-athy, there is a defect in the energy production process. The CHCHD10 gene codes for a protein calledcoiled-coil-helix-coiled-coil-helix domain-containing protein 10 (CHCHD10), which is found in the mito-chondria and is involved in the regulation of mitochondrial function. G58R mutation has been shownto disrupt the normal function of CHCHD10, leading to mitochondrial dysfunction and ultimately tothe development of mitochondrial myopathy. The structures of G58R mutant CHCHD10 and howG58R mutation impacts the wild-type CHCHD10 protein at the monomeric level are unknown. Toaddress this problem, we conducted homology modeling, multiple run molecular dynamics simula-tions and bioinformatics calculations. We represent herein the structural ensemble properties of theG58R mutant CHCHD10 (CHCHD10G58R) in aqueous solution. Moreover, we describe the impacts ofG58R mutation on the structural ensembles of wild-type CHCHD10 (CHCHD10WT) in aqueous solution.The dynamics properties as well as structural properties of CHCHD10WTare impacted by the mitochon-drial myopathy-related G58R mutation. Specifically, the secondary and tertiary structure properties,root mean square fluctuations, Ramachandran diagrams and results from principal component analysisdemonstrate that the CHCHD10WTand CHCHD10G58Rproteins possess different structural ensemblecharacteristics and describe the impacts of G58R mutation on CHCHD10WT. These findings may behelpful for designing new treatments for mitochondrial myopathy.