Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow, Russia.
Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow, Russia.
Int J Biol Macromol. 2019 Nov 1;140:736-748. doi: 10.1016/j.ijbiomac.2019.08.178. Epub 2019 Aug 21.
α-Crystallin maintains the transparency of the lens by preventing the aggregation of damaged proteins. The aim of our work was to study the chaperone-like activity of native α-crystallin in near physiological conditions (temperature, ionic power, pH) using UV-damaged β-crystallin as the target protein. α-Crystallin in concentration depended manner inhibits the aggregation of UV-damaged β-crystallin. DSC investigation has shown that refolding of denatured UV-damaged β-crystallin was not observed under incubation with α-crystallin. α-Crystallin and UV-damaged β-crystallin form dynamic complexes with masses from 75 to several thousand kDa. The content of UV-damaged β-crystallin in such complexes increases with the mass of the complex. Complexes containing >10% of UV-damaged β-crystallin are prone to precipitation whereas those containing <10% of the target protein are relatively stable. Formation of a stable 75 kDa complex is indicative of α-crystallin dissociation. We suppose that α-crystallin dissociation is the result of an interaction of comparable amounts of the chaperone-like protein and the target protein. In the lens simultaneous damage of such amounts of protein, mainly β and gamma-crystallins, is impossible. The authors suggest that in the lens rare molecules of the damaged protein interact with undissociated oligomers of α-crystallin, and thus preventing aggregation.
α-晶状体蛋白通过阻止受损蛋白质的聚集来保持晶状体的透明性。我们的工作旨在研究天然α-晶状体蛋白在接近生理条件（温度、离子强度、pH 值）下的伴侣样活性，使用紫外线损伤的β-晶状体蛋白作为靶蛋白。α-晶状体蛋白以浓度依赖的方式抑制紫外线损伤的β-晶状体蛋白的聚集。DSC 研究表明，在与α-晶状体蛋白孵育时，未观察到变性的紫外线损伤的β-晶状体蛋白的重折叠。α-晶状体蛋白和紫外线损伤的β-晶状体蛋白形成动态复合物，分子量从 75 到几千 kDa 不等。这种复合物中紫外线损伤的β-晶状体蛋白的含量随复合物的分子量增加而增加。含有>10%紫外线损伤的β-晶状体蛋白的复合物容易沉淀，而含有<10%靶蛋白的复合物则相对稳定。形成稳定的 75 kDa 复合物表明α-晶状体蛋白解离。我们假设α-晶状体蛋白的解离是由于相当数量的伴侣样蛋白和靶蛋白相互作用的结果。在晶状体中，同时损伤如此大量的蛋白质，主要是β和γ-晶状体蛋白，是不可能的。作者提出，在晶状体中，少量受损的蛋白质分子与未解离的α-晶状体蛋白寡聚物相互作用，从而阻止聚集。
