Abstract
The current study was performed with the aim to evaluate the chaperoning ability, structural features, and aggregation propensity of wild-type and R12C mutant αB-crystallins (αB-Cry) under thermal stress and in the presence of calcium ion. The results of different spectroscopic analyses suggest that wild-type and mutant αB-Cry have dissimilar secondary and tertiary structures. Moreover, αB-Cry indicates slightly improved chaperone activity upon the R12C mutation. Thermal stress and calcium, respectively, enhance and reduce the extent of solvent-exposed hydrophobic surfaces accompanying formation of ordered and non-ordered aggregate entities in both proteins. Compared to the wild-type protein, the R12C mutant counterpart shows significant resistance against thermal and calcium-induced aggregation. In addition, in the presence of calcium, significant structural variation was accompanied by reduction in the solvent-exposed hydrophobic patches and attenuation of chaperone activity in both proteins. Additionally, gel mobility shift assay indicates the intrinsic propensity of R12C mutant αB-Cry for disulfide bridge-mediated protein dimerization. Overall, the results of this study are of high significance for understanding the molecular details of different factors that are involved in the pathomechanism of cataract disorders.
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Published in Russian in Biokhimiya, 2016, Vol. 81, No. 2, pp. 215–230.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM15-282, December 27, 2015.
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Ragerdi Kashani, M., Yousefi, R., Akbarian, M. et al. Structure, chaperone activity, and aggregation of wild-type and R12C mutant αB-crystallins in the presence of thermal stress and calcium ion – Implications for role of calcium in cataract pathogenesis. Biochemistry Moscow 81, 122–134 (2016). https://doi.org/10.1134/S0006297916020061
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DOI: https://doi.org/10.1134/S0006297916020061