Molecular Structure and Function of Crystallins

晶状体蛋白的分子结构和功能

• 批准号: 8938290
• 负责人: graeme j wistow
• 金额: $ 18.18万
• 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/8938290
• 关键词: Adopted; Aging; Amino Acids; Animal Model; Behavior; Birds; Blindness; Cataract; Cell physiology; Characteristics; Chickens; Crystallins; Degenerative Disorder; Development; Environment; Exhibits; Eye; Failure; Family; Family member; Fish Proteins; Human; Lead; Light; Modeling; Molecular Chaperones; Molecular Structure; Pathway interactions; Process; Processed Genes; Property; Proteins; Recombinants; Refractive Indices; Role; Solutions; Staging; Stress; Structure; Tissues; Work; Zebrafish; amyloid formation; biophysical properties; gamma-Crystallins; lens; protein folding

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.

在人和动物模型中，γ-晶体蛋白与白内障有关。 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代表该家族在组成和行为上的极端的蛋白质。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，适合高蛋白浓度环境，并揭示了它们在压力下如何展开。对鸡gS-晶体蛋白的研究表明，鸟类祖先中单个氨基酸的变化如何显着影响蛋白质的结构和稳定性。这种蛋白质在溶液中也表现出显着的特性，这表明它可能是展开过程中某个阶段的模型。这项工作和其他工作揭示了涉及晶体蛋白的解折叠和淀粉样蛋白形成的过程，以及α-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NMR结构分析已用于确定来自斑马鱼的gM 7-晶体蛋白的第一结构，其在组成和行为方面代表该家族的极端成员。该结构通常是保守的，但说明了一些特定的变化所产生的关键残基的替代，显示这些残基如何有助于人类γ-晶体蛋白的紧密折叠的结构。