Conformational change and destabilization of cataract γC‐crystallin T5P mutant

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Abstract
Human lens γC‐crystallin and T5P mutant were cloned, and their biophysical properties and thermodynamic stability were studied. CRYGC (T5P) is one of the many γ‐crystallin mutant genes for autosomal dominant congenital cataracts. This mutation is associated with Coppock‐like cataract, and has the phenotype of a dust‐like opacity of the fetal lens nucleus. During cloning and overexpression, the majority of T5P mutant was found in the inclusion body. This property is unique among the many cataract γ‐crystallin mutant genes. It is thus worthwhile to study what factors contribute to this unique property of γC‐crystallin. One possibility is changes in conformation and stability, which can be studied using spectroscopic measurements. In this study, conformational change was studied by circular dichroism and fluorescence measurements, and conformational stability was determined by thermal unfolding probed by Trp fluorescence and time‐dependent light scattering. The T5P mutation obviously changes conformation and decreases conformational stability.