Faculty of Sciences, Department of Physics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
J Biomol Struct Dyn. 2024 Jul;42(11):5607-5616. doi: 10.1080/07391102.2023.2227713. Epub 2023 Jun 22.
The mitochondria are responsible for producing energy within the cell, and in mitochondrial myopathy, there is a defect in the energy production process. The CHCHD10 gene codes for a protein called coiled-coil-helix-coiled-coil-helix domain-containing protein 10 (CHCHD10), which is found in the mitochondria and is involved in the regulation of mitochondrial function. G58R mutation has been shown to disrupt the normal function of CHCHD10, leading to mitochondrial dysfunction and ultimately to the development of mitochondrial myopathy. The structures of G58R mutant CHCHD10 and how G58R mutation impacts the wild-type CHCHD10 protein at the monomeric level are unknown. To address this problem, we conducted homology modeling, multiple run molecular dynamics simulations and bioinformatics calculations. We represent herein the structural ensemble properties of the G58R mutant CHCHD10 (CHCHD10) in aqueous solution. Moreover, we describe the impacts of G58R mutation on the structural ensembles of wild-type CHCHD10 (CHCHD10) in aqueous solution. The dynamics properties as well as structural properties of CHCHD10 are impacted by the mitochondrial myopathy-related G58R mutation. Specifically, the secondary and tertiary structure properties, root mean square fluctuations, Ramachandran diagrams and results from principal component analysis demonstrate that the CHCHD10 and CHCHD10 proteins possess different structural ensemble characteristics and describe the impacts of G58R mutation on CHCHD10. These findings may be helpful for designing new treatments for mitochondrial myopathy.Communicated by Ramaswamy H. Sarma.
线粒体负责在细胞内产生能量，而在线粒体肌病中，能量产生过程存在缺陷。CHCHD10 基因编码一种叫做卷曲螺旋-螺旋-卷曲螺旋-卷曲螺旋结构域蛋白 10（CHCHD10）的蛋白质，该蛋白质存在于线粒体中，参与调节线粒体功能。已经表明 G58R 突变会破坏 CHCHD10 的正常功能，导致线粒体功能障碍，最终导致线粒体肌病的发生。G58R 突变体 CHCHD10 的结构以及 G58R 突变如何在单体水平上影响野生型 CHCHD10 蛋白的结构尚不清楚。为了解决这个问题，我们进行了同源建模、多次分子动力学模拟和生物信息学计算。我们在此代表 G58R 突变体 CHCHD10（CHCHD10）在水溶液中的结构集合特性。此外，我们描述了 G58R 突变对水溶液中野生型 CHCHD10（CHCHD10）结构集合的影响。动力学特性以及 CHCHD10 的结构特性受到与线粒体肌病相关的 G58R 突变的影响。具体来说，二级和三级结构特性、均方根波动、拉马钱德兰图和主成分分析的结果表明，CHCHD10 和 CHCHD10 蛋白具有不同的结构集合特征，并描述了 G58R 突变对 CHCHD10 的影响。这些发现可能有助于设计线粒体肌病的新治疗方法。由 Ramaswamy H. Sarma 交流。
