肌萎缩侧索硬化
拉马钱德兰地块
突变体
失智症
突变
C9orf72
蛋白质结构
遗传学
螺旋(腹足类)
蛋白质二级结构
野生型
生物
化学
结晶学
基因
生物化学
痴呆
医学
三核苷酸重复扩增
疾病
病理
生态学
等位基因
蜗牛
作者
Hakan Alıcı,Vladimir N. Uversky,David E. Kang,Jung A. Woo,Orkid Coskuner
标识
DOI:10.1021/acschemneuro.2c00011
摘要
The S59L genetic mutation of the mitochondrial coiled-coil-helix-coiled-coil-helix domain-containing protein 10 (CHCHD10) is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The wild-type and mutant forms of this protein contain intrinsically disordered regions, and their structural characterization has been facing challenges. Here, for the first time in the literature, we present the structural ensemble properties of the wild-type and S59L mutant form of CHCHD10 in an aqueous solution environment at the atomic level with dynamics. Even though available experiments suggested that the S59L mutation may not change the structure of the CHCHD10 protein, our structural analysis clearly shows that the structure of this protein is significantly affected by the S59L mutation. We present here the secondary structure components with their abundances per residue, the tertiary structure properties, the free energy surfaces based on the radius of gyration and end-to-end distance values, the Ramachandran plots, the quantity of intramolecular hydrogen bonds, and the principal component analysis results. These results may be crucial in designing more efficient treatment for ALS and FTD diseases.
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