beta B2 W151R mutant is prone to degradation, aggregation and exposes the hydrophobic side chains in the fourth Greek Key motif

Studies have established that congenital cataract is the major cause of blindness in children across the globe. The beta-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 beta B2 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 beta B2 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.

Automated summary

Congenital cataract is a major cause of blindness in children globally. A novel beta B2 mutation W151R was found to be prone to aggregation due to low solubility and poor structural stability, but the negative effect of the mutation was reversed by administration of lanosterol.