Molecular Structure and Function of Crystallins

在人和动物模型中，γ-晶体蛋白与白内障有关。gS-晶状体蛋白是成人透镜中主要的bg-晶状体蛋白，并且还发现在黄斑变性模型的视网膜色素上皮中被诱导。在小鼠中，gS基因已被切除，导致正常纤维细胞成熟的破坏。这与纤维细胞结构的关键组分的异常有关，表明晶状体蛋白在维持透镜和眼睛其他地方的细胞结构中的功能作用。实验正在进行中，以直接测量gS在组装关键细胞结构中的可能作用。对老年敲除小鼠的检查也为眼睛其他部位的缺陷提供了证据，这些缺陷可能为衰老提供了模型。 使用NMR结构分析的合作研究揭示了小鼠gS突变体Opj的解折叠和淀粉样蛋白形成过程。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。

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. This is associated with abnormalities in key components of the architecture of the fiber cells, suggesting a functional role for crystallins in maintaining cell structure both in lens and elsewhere in the eye. Experiments are underway to measure directly the possible role of gS in assembly of key cellular structures. Examination of older knockout mice is also providing evidence for defects in other parts of the eye that may provide a model for aging. Collaborative studies using NMR structure analysis are shedding light on the processes of unfolding and amyloid formation in the mouse gS mutant Opj. This has wider significance for understanding how normally folded proteins can unfold and adopt other structures that can have serious consequences for cellular function.