Effects of the Jokela type of spinal muscular atrophy‐related G66V mutation on the structural ensemble characteristics of CHCHD10

The G66V pathological variant of the coiled‐coil‐helix‐coiled‐coil‐helix domain‐containing protein 10 (CHCHD10), mitochondrial, plays a role in Jokela type spinal muscular atrophy. The wild‐type and G66V mutant‐type CHCHD10 proteins contain intrinsically disordered regions, and therefore, their structural ensemble studies have been experiencing difficulties using conventional tools. Here, we show our results regarding the first characterization of the structural ensemble characteristics of the G66V mutant form of CHCHD10 and the first comparison of these characteristics with the structural ensemble properties of wild‐type CHCHD10. We find that the structural properties, potential of mean force surfaces, and principal component analysis show stark differences between these two proteins. These results are important for a better pathology, biochemistry and structural biology understanding of CHCHD10 and its G66V genetic variant and it is likely that these reported structural properties are important for designing more efficient treatments for the Jokela type of spinal muscular atrophy disease.

线粒体的G66V病理变异（CHCHD10）在Jokela型脊柱肌肉萎缩中起着作用。我们展示了有关第一个表征的结果CHCHD10的G66V突变体形式的结构集合特征以及这些特征与野生型CHCHD10的结构集合特性的首次比较。遗传变异，这些报道的结构特性对于设计更有效的Jokela类型的脊柱肌肉萎缩疾病的治疗很重要。