Weininger Susanne, Neudorf Malte, Gröger Stefan, Plato Eric, Broneske Robert, Saalwächter Kay, Weininger Ulrich, Balbach Jochen
Martin Luther University Halle-Wittenberg, Institute of Physics, Betty-Heimann-Strasse 7, DE-06120, Halle, Germany.
Macromol Biosci. 2023 May;23(5):e2200526. doi: 10.1002/mabi.202200526. Epub 2023 Mar 12.
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 cause cataract. γD-crystallin (hγD) is involved in the energy dissipation of absorbed UV light by energy transfer between aromatic side chains. Early UV-B induced damage of hγD with molecular resolution is studied by solution NMR and fluorescence spectroscopy. hγD modifications are restricted to Tyr 17 and Tyr 29 in the N-terminal domain, where a local unfolding of the hydrophobic core is observed. None of the tryptophan residues assisting fluorescence energy transfer is modified and hγD is remained soluble over month. Investigating isotope-labeled hγD surrounded by eye lens extracts from cataract patients reveals 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 shows under the here used conditions a thermodynamic stability comparable to the wild type but an increased sensitivity toward UV-B irradiation.
在人眼晶状体中，晶状体蛋白有助于实现透明度、光折射以及紫外线防护功能。α-、β-和γ-晶状体蛋白之间失调的平衡相互作用会导致白内障。γD-晶状体蛋白（hγD）通过芳香族侧链之间的能量转移参与吸收的紫外线的能量耗散。利用溶液核磁共振和荧光光谱法对早期紫外线B诱导的hγD损伤进行了分子分辨率研究。hγD的修饰仅限于N端结构域中的酪氨酸17和酪氨酸29，在该区域观察到疏水核心的局部解折叠。协助荧光能量转移的色氨酸残基均未被修饰，并且hγD在数月内仍保持可溶状态。对来自白内障患者晶状体提取物包围的同位素标记hγD进行研究发现，C端hγD结构域中暴露于溶剂的侧链之间的相互作用非常微弱，并且提取物仍具有一些光保护特性。在患白内障的婴儿晶状体核心中发现的遗传性E107A hγD在本文所用条件下显示出与野生型相当的热力学稳定性，但对紫外线B照射的敏感性增加。
