关键词： Cataract-causing mutation Protein aggregation Protein degradation βB2-crystallin

Mesh ： Cataract / congenital drug therapy genetics pathology Child, Preschool DNA Mutational Analysis Female HEK293 Cells HeLa Cells Humans Hydrophobic and Hydrophilic Interactions / drug effects Lanosterol / pharmacology therapeutic use Lens, Crystalline / drug effects pathology Male Molecular Dynamics Simulation Mutagenesis, Site-Directed Mutation Pedigree Protein Aggregation, Pathological / congenital drug therapy genetics Protein Conformation, beta-Strand / drug effects genetics Proteolysis / drug effects Recombinant Proteins / chemistry genetics isolation & purification metabolism Trypsin / metabolism beta-Crystallin B Chain / chemistry genetics isolation & purification metabolism

来  源：   DOI：10.1016/j.bbadis.2020.166018   PDF(Sci-hub)

Abstract：
Studies have established that congenital cataract is the major cause of blindness in children across the globe. The β-crystallin protein family is the richest and most soluble structural protein in the lens. Their solubility and stability are essential in maintaining lens transparency. In this study, we identified a novel βB2 mutation W151R in a rare progressive cortical congenital cataract family and explored its pathogenesis using purified protein and mutant related cataract-cell models. Due to its low solubility and poor structural stability, the βB2 W151R mutation was prone to aggregation. Moreover, the W151R mutation enhanced the exposure of the hydrophobic side chains in the fourth Greek Key motif, which were readily degraded by trypsin. However, upon the administration of lanosterol, the negative effect of the W151R mutation was reversed. Therefore, lanosterol is a potential therapeutic option for cataracts.
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