{Reference Type}: Journal Article
{Title}: Congenital cataract-causing mutation βB1-L116P is prone to amyloid fibrils aggregation and protease degradation with low structural stability.
{Author}: Liu J;Xu W;Wang K;Chen F;Ren L;Xu J;Yao K;Chen X;
{Journal}: Int J Biol Macromol
{Volume}: 195
{Issue}: 0
{Year}: Jan 2022 15
{Factor}: 8.025
{DOI}: 10.1016/j.ijbiomac.2021.12.044
{Abstract}: Congenital cataract, a common disease with lens opacification, causes blindness in the newborn worldwide and is mainly caused by abnormal aggregation of crystallin. As the main structural protein in the mammalian lens, βB1-crystallin has an important role in the maintenance of lens transparency. Recently, the L116P mutation in βB1-CRY was found in a Chinese family with congenital nuclear cataracts, while its underlying pathogenic mechanism remains unclear. In the current study, the βB1 wild-type protein was purified, and the mutated form, βB1-L116P, was examined for examining the effect on structural stability and susceptibility against environmental stresses. Our results reveal low solubility and structural stability of βB1-L116P at physiological temperature, which markedly impaired the protein structure and the oligomerization of βB1-crystallin. Under guanidine hydrochloride-induced denaturing conditions, βB1-L116P mutation perturbed the protein unfolding process, making it prone to amyloid fibrils aggregation. More importantly, the L116P mutation increased susceptibility of βB1-crystallin against UV radiation. βB1-L116P overexpression led to the formation of more serious intracellular aggresomes under UV radiation or oxidative stress. Furthermore, the βB1-L116P mutation increased the sensitivity to the proteolysis process. These results indicate that the low structural stability, susceptibility to amyloid fibrils aggregation, and protease degradation of βB1-L116P may contribute to cataract development and associated symptoms.