Researchers from Turkey and the US unraveled the structural ensemble characteristics of a pathological variant of the CHCHD10 protein associated with Jokela-type spinal muscular atrophy (SMA) for the first time. 

The researchers reported “stark differences” between the mutant and wild-type proteins in terms of structural properties, the potential of mean force surfaces, and principal components, the authors noted. They said that their findings are important as they can help better understand the pathology, biochemistry, and structural biology of CHCHD10 and its pathological G66V variant and could help researchers develop new and more efficient treatments for Jokela type SMA in the future.

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The study is published in the journal Proteins.

Because the wild-type and G66V variants of the CHCHD10 protein contain intrinsically disordered regions, it has, so far, been difficult to conduct structural ensemble studies using conventional tools.

Here, a team led by Orkid Coskuner-Weber, PhD, from the Turkish-German University in Istanbul, Türkiye, used multiple run molecular dynamics simulations and the Iterative Threading ASSembly Refinement homology modeling method to identify the structural ensemble properties of the wild-type and mutant CHCHD10 proteins.

The researchers found that the G66V genetic mutation affected the alpha-helix and beta-sheet formations of wild-type CHCHD10, but that it did not have an impact on the compactness of the protein.

The researchers also found that the number of hydrogen bonds was similar between the 2 versions of the protein but that the interactions between the C-, mid, and N-terminus domains of the proteinwere weaker or inexistent in the G66V mutant. Finally, the team found broad changes in protein–protein interactions of the G66V variant.

Jokela-type SMA, also known as late-onset spinal motor neuronopathy is a slow-progressing form of SMA caused by a mutation in the CHCHD10 gene. Symptoms of Jokela-type SMA usually appear around 30 to 40 years of age and include muscle cramps and weakness, especially in the legs causing difficulty walking. CHCHD10 is a mitochondrial protein the role of which is not fully understood.


Alici H, Uversky VN, Kang DE, et al. Effects of the Jokela type of spinal muscular atrophy-related G66V mutation on the structural ensemble characteristics of CHCHD10. Proteins. Published online January 10, 2023. doi:10.1002/prot.26463