γ-Crystallin redox-detox in the lens

Abstract

In the vertebrate eye, limiting oxidation of proteins and lipids is key to maintaining lens function and avoiding cataract formation. A study by Serebryany et al. identifies a surprising contributor to the eye's oxidative defense in their demonstration that γD-crystallin (HγD) functions as an oxidoreductase and uses disulfide exchange to initiate aggregation of mutant crystallins that mimic oxidative damage. These insights suggest a mechanism by which a dynamic pool of closely packed proteins might avoid oxidation-driven protein-folding traps, providing new avenues to understand the basis of a human disease with global impact.

Figure 1.

Model for disulfide transfer from oxidized HγD to reduced W42Q HγD. The Cys¹⁰⁸–Cys¹⁰⁰ and Cys³²–Cys⁴¹ potential disulfides in HγD are shown. The Trp to Gln mutation adjacent to Cys⁴¹ is shown in red.