Molecular Structure and Function of Crystallins

-晶体蛋白在人和动物模型中都与白内障有关。gs -晶状体蛋白是成人晶状体中主要的gs -晶状体蛋白，在黄斑变性模型中，gs -晶状体蛋白也被发现在视网膜色素上皮中被诱导。gS基因在小鼠中被切除，导致正常纤维细胞成熟被破坏。确定gS相互作用伙伴的酵母2杂交实验正在进行中。小鼠gs -晶体蛋白的核磁共振结构分析表明，柔性连接体和n端区域在蛋白质溶解度的熵贡献中起重要作用。我们还发现突变蛋白在Opj晶状体中形成淀粉样斑块。与小鼠Opj白内障相关的突变gS的结构现在正在被确定，并正在揭示蛋白质展开的过程。这对其他蛋白质折叠疾病如淀粉样蛋白疾病也有启示。

gamma-crystallins are associated with cataract in both human and animal models. gS-crystallin is the major bg-crystallin in the adult human lens and has also been found to be induced in retinal pigment epithelium in models of macular degeneration. The gene for gS has been ablated in mouse, leading to disruption of normal fiber cell maturation. Yeast 2-hybrid experiments to determine interaction partners for gS are in progress. NMR structure analysis of mouse gS-crystallin has shown important roles for flexible linker and N-terminal regions in providing entropic contributions to protein solubility. We have also shown that the mutant protein forms amyloid-like plaques in the Opj lens. The structure of mutant gS associated with the mouse Opj cataract is now being determined and is shedding light on the processes of protein unfolding. This has implications for other protein folding diseases such as amyloid diseases. The structure and stability of g- and beta-crystallins are dependent on a pattern of highly conserved amino acid residues. This sequence signature is also present in non-lens relatives of the crystallins, such as absent in melanoma 1 (AIM1)a protein implication in control of malignancy in melanoma. However proteins like AIM1 which have a lower requirement for stability than crystallins may compromise structural stability for additional functional roles. In collaborative studies we have investigated the structure of the most divergent domain of human AIM1. X-ray analysis shows that the basic structure is conserved, while loss of key residues has loosened parts of the structure.