LAUSR

In the human eye lenses, the crystallin proteins facilitate transparency, light refraction, as well as UV light protection. A deregulated balanced interplay between α-, β-, and γ-crystallin can causes cataract. γD-crystallin (hγD) is involved in the energy dissipation of absorbed UV light by energy transfer between aromatic side chains. We studied early UV-B induced damage of hγD with molecular resolution by solution NMR and fluorescence spectroscopy. hγD modifications were restricted to Tyr 17 and Tyr 29 in the N-terminal domain, where we observed a local unfolding of the hydrophobic core. None of the tryptophan residues assisting fluorescence energy transfer was modified and hγD remained soluble over month. Investigating isotope labeled hγD surrounded by eye lens extracts from cataract patients revealed very week interactions of solvent-exposed side chains in the C-terminal hγD domain and some remaining photoprotective properties of the extracts. Hereditary E107A hγD found in the eye lens core of infants developing cataract showed under the here used conditions a thermodynamic stability comparable to the wild type but an increased sensitivity towards UV-B irradiation. This article is protected by copyright. All rights reserved.