摘要
α-晶体蛋白是晶状体中重要的成份蛋白质,是由αA和αB亚基组成的四聚体蛋白。长期被认为其功能主要是维持晶状体的结构和屈光性,自1992年Horwitz证实α-晶体蛋白具有分子伴侣(molecular chaperone)作用之后,大量的研究表明α-晶体蛋白能够抑制其它晶状体蛋白和酶的化学性修饰和热凝聚而保护其活性,对长期维持晶状体的透明性具有重要作用。αA亚基C-端序列和αB亚基C-端的伸展性的变化以及N-端区域的疏水性是维持α-晶体蛋白伴侣活性的重要因素。晶状体核的α-晶体蛋白具有年龄依赖性分子伴侣作用的降低。α-晶体蛋白翻译后修饰(post-translational modifications,PTM)不同程度地降低分子伴侣作用。分子伴侣作用的下降导致晶状体蛋白的凝聚和酶的失活,加剧了光线散射,从而形成晶状体混浊。寻找分子伴侣作用的保护剂或减少晶状体蛋白翻译后的修饰,将为白内障发病机理和临床防治的研究开辟一个崭新的领域。眼科学报2000;16:91-96。
The a-crystallin is a major structural protein within the lens and consists of two types of subunit, aaaaaA and αB. These subunits propose a model for the quaternary structure of α-crystallin. It has been known for many years that its main function is to serve as a structural and refractive elements in lens. Until 1992, Horwitz suggested that a-crystallin could act in a chaperone-like manner. Many studies have showed that a-crystallin can protect enzymes and other crystallins against both chemically- and thermally-induced inactivation or aggregation, which may play an important role in maintaining transparency of lens. A polypeptide sequence of αA-crystallin or extension of αB-crystallin in C-terminal-region and hydrophobic N-terminal-region are all essential for chaperone function. A decrease in chaperone activity from nuclear crystallin has been showed in age-dependent fashion. Post-translational modifications occurring to α-crystallin with increasing age and during cataract formation may decrease the chaperone activity of a-crystallin to different extent, resulting in an increase in other crystallins aggregation and enzymes inactivation. Therefore, these aggregates will increase scattering of light and lead to lens opacification. Development of protective agents for molecular chaperone activity of a-crystallin, in conjunction with knowledge of decreasing post-translational modifications, could potentially lead to a new field for the research on pathogenesis and clinical treatment of cataract. Eye Science 2000; 16: 91 - 96.
出处
《眼科学报》
2000年第2期91-96,共6页
Eye Science
关键词
Α-晶体蛋白
分子伴侣
转录后修饰
白内障
α-crystallin, molecular chaperon, post-translational modifications, cataract
