Protection of human γD-crystallin protein from ultraviolet C-induced aggregation by ortho-vanillin

Cataract is known as one of the leading causes of vision impairment worldwide. While the detailed mechanism of cataratogenesis remains unclear, cataract is believed to be correlated with the aggregation and/or misfolding of human ocular lens proteins called crystallins. A 173-residue structural protein human gamma D-crystallin is a major gamma-crystallin protein in the human eye lens and associated with the development of juvenile and mature-onset cataracts. This work is aimed at investigating the effect of a small molecule, e.g., ortho-vanillin, on human gamma D-crystallin aggregation upon exposure to ultraviolet-C irradiation. According to the findings of right-angle light scattering, transmission electron microscopy, and gel electrophoresis, ortho-vanillin was demonstrated to dose-dependently suppress ultraviolet-C-triggered aggregation of human gamma D-crystallin. Results from the synchronous fluorescence spectroscopy, tryptophan fluorescence quenching, and molecular docking studies revealed the structural change of gamma D-crystallin induced by the interaction/binding between ortho-vanillin and protein. We believe the outcome from this work may contribute to the development of potential therapeutics for cataract. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the effect of ortho-vanillin on ultraviolet-C-induced aggregation of human gamma D-crystallin, demonstrating its dose-dependent suppression of protein aggregation. Structural changes in gamma D-crystallin induced by the interaction with ortho-vanillin were revealed, potentially contributing to the development of therapeutics for cataracts.