Effects of cataract-causing mutations W59C and W151C on βB2-crystallin structure, stability and folding

beta/gamma-Crystallins, the predominant structural proteins in vertebrate lens with lifelong stability to maintain lens transparency, share a high similarity in their primary sequences and tertiary structures. Four conserved Trp residues have been shown to be important to gamma-crystallin structure, stability and protection against UV irradiation, whereas their roles in beta-crystallins remain elusive. Herein we found that two congenital cataract-causing mutations, W59C and W151C, dramatically decreased beta B2-crystallin solubility and stability against thermal and guanidine hydrochloride-induced denaturation. The two mutated proteins were prone to form aggregates when irradiated by UV light in the tubes or exogenously expressed in the cells. Although W59 and W151 are structurally identical in beta/gamma-crystallin domains, substituting them by Cys led to dissimilar influences on beta B2-crystallin stability. Our results suggested that the conserved Trp residues might play a more crucial role in the correct folding and structural integrity of beta-crystallin domains than in gamma-crystallins. (C) 2017 Elsevier B.V. All rights reserved.