Molecular Structure and Function of Crystallins

在人类和动物模型中，伽马晶体蛋白都与白内障有关。 为了探索g-晶体蛋白的功能特性，已经表达了来自鱼类和鸟类的蛋白质，这些蛋白质在组成和行为上代表了该家族的极端。在几项生物物理研究中使用重组g-晶体蛋白，我们已经证明它们具有非常不寻常的溶液性质，适合于高蛋白浓度环境，并揭示了它们在压力下是如何展开的。对鸡GS-晶体蛋白的研究表明，鸟类远古祖先中单一氨基酸的变化是如何显著影响蛋白质的结构和稳定性的。这种蛋白质在溶液中也表现出显着的性质，这表明它可能是展开过程中的一个阶段的模型。这项工作和其他工作正在揭示涉及晶体蛋白的解折叠和淀粉样蛋白形成的过程，以及a-晶体蛋白的保护性、伴侣作用。这对于理解正常折叠的蛋白质如何展开并采用可能对细胞功能产生严重后果的其他结构具有更广泛的意义。 详细的核磁共振结构分析已经被用来确定斑马鱼gM7-晶体蛋白的第一个结构，从组成和行为上来说，它是该家族的一个极端成员。该结构通常保存得很好，但说明了替换关键残基导致的一些具体变化，表明这些残基是如何促进人类伽马晶体蛋白的紧密折叠结构的。

gamma-crystallins are associated with cataract in both human and animal models. To explore the functional characteristics of g-crystallins, proteins from fish and birds representing the extremes of the family in composition and behavior have been expressed. Using recombinant g-crystallins in several biophysical studies, we have shown that they have highly unusual solution properties that fit them for high protein concentration environments and shed light on how they unfold under stress. Studies on chicken gS-crystallin show how a single amino acid change in ancient ancestors of birds significantly affecetd the structure and stability of the protein. This protein also exhibits remarkable properties in solution that suggest it may be a model for a stage in the process of unfolding. This and other work is shedding light on the processes of unfolding and amyloid formation involving crystallins and the also the protective, chaperone role of a-crystallin. This has wider significance for understanding how normally folded proteins can unfold and adopt other structures that can have serious consequences for cellular function. Detailed NMR structure analysis has been used to determine the first structure of gM7-crystallin from zebrafish, representing an extreme member of the family in terms of composition and behavior. The structure is generally well-conserved but illustrates some specific changes resulting from replacement of key residues that show how those residues contribute to the tightly folded structure of human gamma-crystallins.