LENS INHIBITOR PROTEINS AND CATARACTOGENESIS

透镜中心的蛋白质基质，虽然建立了 在生命的早期，在整个生命中都存在。 根据这些 即使是最轻微的蛋白水解活性的痕迹， 导致这个矩阵的破坏，并可能导致 形成透镜混浊或白内障。 透镜已经 显示含有几种不同的胰蛋白酶样酶，但这些 处于休眠状态。 这种休眠可能代表了 在透镜中有效的胰蛋白酶抑制剂活性的作用。 我们 已经显示了几种不同的胰蛋白酶抑制剂的存在， 透镜。 这种抑制剂活性的大部分是由于其中一种 主要透镜结构蛋白，α-晶状体蛋白。 此多提交 蛋白质能够抑制几个分子的胰蛋白酶， α-晶状体蛋白分子。 α-晶状体蛋白可以结合几种 不同的蛋白酶，但这种结合是非常敏感的， 盐浓度 作为对照的α-晶状体蛋白的性质 将研究用于透镜中蛋白水解的分子。 的 α-晶状体蛋白的结构特性将在以下条件下确定： 多种条件与蛋白酶抑制剂相关 活动 蛋白酶结合位点将通过以下方法确定： α-晶状体蛋白的修饰，暴露的 蛋白酶表面的复合物，并交联到相邻的 亚单位。 众所周知，随着年龄的增长，α-晶状体蛋白 转化成水不溶性形式。 由于这种溶解 蛋白质部分，并已完成，它将有可能 研究了修饰后的结构和缓蚀活性 α-晶状体蛋白 将对所有这些过程进行调查， 控制机制，可能与水平， 老化的人透镜和白内障中的游离和结合阳离子。 有人提出，改变三级结构的α- 晶状体蛋白促进聚集。 这个过程涉及 蛋白质分子之间的静电相互作用， 排除盐和水。 聚集的α-晶状体蛋白 不再能够抑制蛋白酶分子， 盐浓度的增加减少了抑制蛋白酶 分子和增加的盐浓度减少了 剩余的α-晶状体蛋白的抑制剂活性。 这些 条件最终导致活性蛋白酶的存在， 引起透镜蛋白自溶的透镜， 白内障

The protein matrix in the center of the lens, while established early in life, remains present throughout life. Under these conditions even the slightest trace of proteolytic activity could lead to the destruction of this matrix, and may result in the formation of a lens opacity or cataract. The lens have been shown to contain several different trypsin-like enzymes, but these exist in the dormant state. This dormancy may represent the effect of an efficient trypsin inhibitor activity in the lens. We have shown the presence of several different trypsin inhibitors in the lens. The bulk of this inhibitor activity is due to one of the major lens structural proteins, alpha-crystallin. This multi-submit protein is able to inhibit several molecules of trypsin for each alpha-crystallin molecule. Alpha-crystallin can bind several different proteinases but this binding is remarkably sensitive to salt concentration. The properties of alpha-crystallin as a control molecule for proteolysis in the lens will be studied. The structural properties of alpha-crystallin will be determined under a variety of conditions and correlated with proteinase inhibitor activity. The proteinase binding site will be determined by modification of alpha-crystallin, iodination of the exposed proteinase surfaces in the complex, and crosslinking to adjacent subunits. It is known that with aging, alpha-crystallin is converted into a water insoluble form. Since solubilization of this protein fraction and has been accomplished, it will be possible to investigate the structure and inhibitor activity of the modified alpha-crystallin. All of these processes will be investigated for control mechanisms which could be correlated with the levels of free and bound cations in the aging human lens and in cataracts. It is proposed that alterations in the tertiary structure of alpha- crystallin promote aggregation. This process involves electrostatic interactions between protein molecules, leading to the exclusion of salt and water. The aggregated alpha-crystallin is no longer capable of inhibiting proteinase molecules and the increased salt concentration diminishes the inhibiting proteinase molecules and the increased salt concentration diminishes the inhibitor activity of the remaining alpha-crystallin. These conditions eventually lead to the presence of active proteinases in the lens which cause the autolysis of lens proteins seen in cataracts.