ßB2 W151R mutant is prone to degradation, aggregation and exposes the hydrophobic side chains in the fourth Greek Key motif.
Biochim Biophys Acta Mol Basis Dis
; 1867(2): 166018, 2021 02 01.
Article
en En
| MEDLINE
| ID: mdl-33246011
ABSTRACT
Studies have established that congenital cataract is the major cause of blindness in children across the globe. The ß-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 ßB2 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 ßB2 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Catarata
/
Cadena B de beta-Cristalina
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Agregación Patológica de Proteínas
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Lanosterol
/
Cristalino
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2021
Tipo del documento:
Article
País de afiliación:
China