Abstract
In this work, we analyzed 78 mutations in the actin protein that cause the disease nemaline myopathy. We analyzed how these mutations are distributed in important regions of the actin molecule (folding nucleus, core of the filament, amyloidogenic regions, disordered regions, regions involved in interaction with other proteins). It was found that 54 mutations (43 residues) fall into the folding nucleus (Ф ≥ 0.5), 11 mutations (10 residues) into the filament core, 14 mutations into the amyloidogenic regions (11 residues), 14 mutations (9 residues) in the unstructured regions, and 24 mutations (22 residues) in regions involved in interaction with other proteins. It was also found that the occurrence of single mutations G44V, V45F, T68I, P72R, K338I and S350L leads to the appearance of new amyloidogenic regions that are not present in native actin. The largest number of mutations (54 out of 78) occurs in the folding nucleus; these mutations are important for folding and therefore can affect the protein folding rate. We have shown that almost all of the considered mutations are associated with the structural characteristics of the actin molecule, and some of the residues we have considered have several important characteristics.
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This research was funded by the Russian Science Foundation, grant number 19–74-10051.
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Glyakina, A.V., Galzitskaya, O.V. Structural and functional analysis of actin point mutations leading to nemaline myopathy to elucidate their role in actin function. Biophys Rev 14, 1527–1538 (2022). https://doi.org/10.1007/s12551-022-01027-4
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DOI: https://doi.org/10.1007/s12551-022-01027-4