Alici Hakan, Uversky Vladimir N, Kang David E, Woo Junga Alexa, Coskuner-Weber Orkid
Department of Physics, Faculty of Science, Zonguldak Bulent Ecevit University, Zonguldak, 67100, Turkey.
Department of Molecular Medicine and USF Health Byrd Alzheimer`s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Curr Protein Pept Sci. 2025;26(3):201-212. doi: 10.2174/0113892037335036241007043530.
The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10 proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.
This study presents the foundational characterization of the structural features of CHCHD10 and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.
Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.
The reported structural properties hold promise for informing the development of more effective treatments for ALS.
线粒体卷曲螺旋-螺旋结构域包含蛋白10（CHCHD10）的Q108P病理变体与肌萎缩侧索硬化症（ALS）有关。野生型和CHCHD10蛋白均表现出内在无序区域，这给使用传统实验工具进行结构研究带来了挑战。
本研究展示了CHCHD10结构特征的基础表征，并将其与野生型对应物的结构特征进行了比较。我们进行了多次分子动力学模拟和生物信息学分析。
我们的研究结果揭示了这两种蛋白质在结构特性、自由能表面和主成分分析输出方面的明显差异。这些结果在病理学、生物化学和结构生物学方面对理解CHCHD10及其Q108P变体有重大贡献。
所报道的结构特性有望为开发更有效的ALS治疗方法提供信息。
