Cumulative deamidations of the major lens protein γS-crystallin increase its aggregation during unfolding and oxidation.

ABSTRACT: Age-related lens cataract is the major cause of blindness worldwide. The mechanisms whereby crystallins, the predominant lens proteins, assemble into large aggregates that scatter light within the lens, and cause cataract, are poorly understood. Due to the lack of protein turnover in the lens, crystallins are long-lived. A major crystallin, γS, is heavily modified by deamidation, in particular at surface-exposed N14, N76, and N143 to introduce negative charges. In this present study, deamidated γS was mimicked by mutation with aspartate at these sites and the effect on biophysical properties of γS was assessed via dynamic light scattering, chemical and thermal denaturation, hydrogen-deuterium exchange, and susceptibility to disulfide cross-linking. Compared with wild type γS, a small popul

SUBMITTER: Vetter CJ 

PROVIDER: S-EPMC7454558 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature