Molecular Structure and Function of Crystallins

晶状体蛋白的分子结构和功能

• 批准号: 8339746
• 负责人: graeme j wistow
• 金额: $ 76.37万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8339746
• 关键词: Adopted; Adult; Aging; Animal Model; Architecture; Behavior; Birds; Blindness; Cataract; Cell Maturation; Cell physiology; Cellular Structures; Characteristics; Crystallins; Defect; Degenerative Disorder; Development; Eye; Eye Part; Failure; Family; Fish Proteins; Genes; Human; Knockout Mice; Lead; Light; Macular degeneration; Measures; Modeling; Molecular Structure; Mus; Pathway interactions; Process; Processed Genes; Property; Proteins; Refractive Indices; Role; Structure; Structure of retinal pigment epithelium; Techniques; Tissues; amyloid formation; fiber cell; gamma-Crystallins; lens; mutant; protein folding; research study

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. 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 and are being compared by several biophysical techniques.

γ-结晶蛋白在人类和动物模型中都与白内障有关。 GS-晶状蛋白是成年人晶状体中的主要BG-晶状体蛋白，也发现在黄斑变性模型中是在视网膜色素上皮中诱导的。 GS的基因已在小鼠中消融，导致正常纤维细胞成熟的破坏。这与纤维细胞结构的关键成分异常有关，这表明晶体蛋白在维持眼镜和其他地方的细胞结构中的功能作用。正在进行实验，直接测量GS在关键细胞结构组装中的可能作用。对旧敲除小鼠的检查还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模型。 使用NMR结构分析的协作研究揭示了小鼠GS突变体OPJ中展开和淀粉样蛋白形成的过程。这对于理解通常折叠蛋白如何展开并采用其他可能对细胞功能产生严重后果的结构具有更大的意义。 为了探索G-晶状体的功能特征，已经表达了代表家庭极端的鱼类和代表家族极端的蛋白质，并通过几种生物物理技术进行了比较。