AGE & CATARACT RELATED CHANGES IN LENS PROTEIN STRUCTURE

镜头透明度是通过保持结构的规律性实现的 细胞质蛋白和纤维细胞膜的均匀排列。 光散射在这两个层次的结构中被最小化 规律性。年龄和白内障依赖的蛋白质和蛋白质变化 膜，在相互作用性质或结构中，将 改变结构规律性，造成晶状体混浊。蛋白 晶状体中的浓度非常高，它们与 彼此之间。这种相互作用提供了结构规律性。在……里面 相比之下，导致高分子量(HMW)的相互作用 集合体破坏了结构的规律性。两者的作用机制 相互作用还没有被很好地理解。HMW的形成 聚集似乎是由蛋白质展开启动的，在 语篇转换是由翻译后修饰引起的。这个过程 似乎是这样的；翻译后的修饰导致了 展开导致聚集，导致不溶解。这个 聚集可以是蛋白质-蛋白质，也可以是蛋白质-膜。 互动。这些事件最终会导致镜头混浊。它是 然而，尚不清楚翻译后的修改是如何展开的 蛋白质，以及未折叠的蛋白质如何变得容易 聚合。它还需要确定如何聚合 不溶性蛋白质在散射光方面变得如此有效 不透明的镜片。在这项拟议的研究中， 我们将首先研究正常的蛋白质相互作用，然后 被HMW打乱并取而代之的机制 聚合。要使用的技术包括荧光， 圆二色谱和核磁共振。不仅可以--研究 蛋白质的展开过程，也是结构上的变化 聚集的和不溶的蛋白质。后者似乎是一种 是光散射的重要贡献者，可以通过 前表面荧光和固体核磁共振。另一项重要的 影响晶状体混浊的因素是膜的变化。一个 膜刚性的增加不仅影响生物 函数，但也会更改物理属性，如 折射率。测量荧光各向异性和 会做微粘度来了解增加的效果 胆固醇和相关晶体蛋白。 这项拟议的研究的意义在于它提出了一些 重视蛋白质浓缩液的研究 爽身粉和镜片凝胶。研究从稀溶液到 浓缩液，最后到透镜，可以提供信息 与活体内实际发生的情况更相关。

Lens transparency is achieved by maintain structural regularity of cytoplasmic proteins and uniform alignment of fiber cell membranes. Light scattering is minimized of these two levels of structural regularity. Age and cataractous dependent changes in proteins and membranes, in the interaction properties or in structures, will alter structural regularity and cause lens turbidity. Protein concentrations in the lens are, very high and they interact with each other. This interaction provides structural regularity. In contrast, the interaction leading to high molecular weight (HMW) aggregate disrupts the structural regularity. The mechanism of both interactions are not well understood. The formation of HMW aggregate appears to be initiated by protein unfolding, which in turn is caused by post-translational modifications. The process appears to be in the order; post-translational modifications leads to unfolding leads to aggregation leads to insolubilization. The aggregation could be either a protein-protein or a protein-membrane interaction. These events finally lead to lens opacity. It is unknown, however, how the post-translational modifications unfold protein, and how the unfolded protein becomes susceptible to aggregation. It also needs to be established how the aggregated and insoluble proteins become so effective in scattering light in the opaque lens. In this proposed study, the mechanism of the normal protein interactions will be studied first, and then the mechanism in which they are disrupted and replaced by HMW aggregation. The techniques to be used include fluorescence, circular dichroism and NMR. It is not only possible to -study the protein unfolding process, but also structural changes in the aggregated and insoluble proteins. The latter one appears to be an important contributor to light scattering and could be studied by front surface fluorescence and solid-state NMR. Another important factor for lens opacification is the change in membranes. An increased membrane rigidity not only affects the biological functions, but also changes the physical properties such as the refractive index. Measuring fluorescence anisotropy and microviscosity will be done to understand the effect of increased cholesterol and associated-crystallins. The significance of this proposed study is that it puts some emphasis on the study of concentrated protein solution,.protein powder and lens gel. Studies progressing from dilute solution to concentrated solution, and finally to lens, may provide information more relevant to what really occurs in vivo.