Schauerte J A, Gafni A
Institute of Gerontology, University of Michigan, Ann Arbor 48109, USA.
Biochem Biophys Res Commun. 1995 Jul 26;212(3):900-5. doi: 10.1006/bbrc.1995.2054.
The major eye-lens protein alpha-crystallin is known to possess a remarkable sequence homology to the low molecular weight heat-shock proteins and has been shown to protect several proteins against thermally induced aggregation. In this work we demonstrate that the rapid aggregation of rabbit muscle phosphoglycerate kinase during incubation at 52 degrees C is completely inhibited in presence of 1/3 moles alpha-crystallin monomer per mole enzyme. Upon irradiation by UV light, tryptophan fluorescence intensity of alpha-crystallin declines, reflecting the destruction of these residues. A remarkable correlation is revealed between the reduction in alpha-crystallin fluorescence during UV-irradiation and the loss of its ability to protect phosphoglycerate kinase against aggregation. Since a loss of tryptophan fluorescence in intact eye lenses in vivo has been demonstrated to occur upon exposure to UV light, as well as during aging, it is proposed that the enhanced rate of lens opacification and cataract formation, as well as the increased levels of damaged lens proteins, which accumulate under these conditions, are the result of the gradual loss of the chaperone-protein efficacy of alpha-crystallin.
主要的晶状体蛋白α-晶体蛋白与低分子量热休克蛋白具有显著的序列同源性，并且已被证明能保护多种蛋白质免受热诱导的聚集。在这项研究中，我们证明，在每摩尔酶存在1/3摩尔α-晶体蛋白单体的情况下，兔肌肉磷酸甘油酸激酶在52℃孵育期间的快速聚集被完全抑制。经紫外线照射后，α-晶体蛋白的色氨酸荧光强度下降，这反映了这些残基的破坏。紫外线照射期间α-晶体蛋白荧光的降低与其保护磷酸甘油酸激酶不发生聚集的能力丧失之间存在显著相关性。由于已证明在体内完整晶状体中，色氨酸荧光的丧失会在暴露于紫外线时以及衰老过程中发生，因此有人提出，晶状体浑浊和白内障形成速率的加快，以及在这些条件下积累的受损晶状体蛋白水平的增加，是α-晶体蛋白伴侣蛋白功效逐渐丧失的结果。
