Congenital cataract is a major cause of childhood blindness worldwide, with crystallin mutations accounting for over 40 % of gene-mutation-related cases. Our research focused on a novel R114C mutation in a Chinese family, resulting in bilateral coronary cataract with blue punctate opacity. Spectroscopic experiments revealed that βA3-R114C significantly altered the senior structure, exhibiting aggregation, and reduced solubility at physiological temperature. The mutant also displayed decreased resistance and stability under environmental stresses such as UV irradiation, oxidative stress, and heat. Further, cellular models confirmed its heightened sensitivity to environmental stresses. These data suggest that the R114C mutation impairs the hydrogen bond network and structural stability of βA3-crystallin, particularly at the boundary of the second Greek-key motif. This study revealed the pathological mechanism of βA3-R114C and may help in the development of potential treatment strategies for related cataracts.
Keywords: Aggregation; Cataract-causing mutation; Environmental stress; Structural stability; βA1/βA3-crystallin.
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