Dynamic disulfide exchange in a crystallin protein in the human eye lens promotes cataract-associated aggregation.

ABSTRACT: Increased light scattering in the eye lens due to aggregation of the long-lived lens proteins, crystallins, is the cause of cataract disease. Several mutations in the gene encoding human γD-crystallin (HγD) cause misfolding and aggregation. Cataract-associated substitutions at Trp⁴² cause the protein to aggregate in vitro from a partially unfolded intermediate locked by an internal disulfide bridge, and proteomic evidence suggests a similar aggregation precursor is involved in age-onset cataract. Surprisingly, WT HγD can promote aggregation of the W42Q variant while itself remaining soluble. Here, a search for a biochemical mechanism for this interaction has revealed a previously unknown oxidoreductase activity in HγD. Using in vitro oxidation, mutational analysis,

SUBMITTER: Serebryany E 

PROVIDER: S-EPMC6240864 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature