THREE-DIMENSIONAL STRUCTURE OF CYTOKINES, RECEPTORS AND IMMUNE SYSTEM PROTEINS

细胞因子、受体和免疫系统蛋白的三维结构

• 批准号: 3776344
• 负责人: D R DAVIES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 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/3776344
• 关键词: X ray crystallography; antibody specificity; antigen antibody reaction; dimer; immune complex; lysozyme; monoclonal antibody; mutant; neurotrophic factors; platelet derived growth factor; protein folding; protein structure; transforming growth factors

1) The crystal structure of the multifunctional cytokine, Transforming Growth Factor-beta (TGF-beta 2), has now been refined to 1.8A resolution. The molecule is a homodimer, with each subunit having an unusual open fold with a preserved disulfide-rich core. Comparison with other members of the TGF-beta family and with the members of the superfamily such as activins and inhibins indicate that they probably adopt very similar structures. The folding topology is also similar to that adopted by Nerve Growth Factor (NGF), and of Platelet Derived Growth Factor (PDGF), although the mode of dimer formation is quite different for all three proteins. 2) As part of an investigation of the structural basis of antibody specificity, the crystal structure of the complex of the MAB HyHEL-5 with chicken lysozyme has been refined. Also, the structure of the complex of this antibody with a mutant lysozyme with 10,000 times weaker binding has been determined. In the mutant an arginine present in the wild type has been replaced by a lysine (R68K). A comparison of the mutant and the wild type has been made in order to explain the large effect of this conservative mutation on the affinity.

1)多功能细胞因子转化酶的晶体结构 生长因子-β（TGF-β 2），现已被细化到1.8A 分辨率 该分子是同二聚体，其中每个亚基具有一个 不寻常的开放褶皱，保存着富含二硫化物的核心。 相比 TGF-β家族的其他成员和TGF-β家族的成员 超家族如激活素和抗肿瘤素表明它们可能 采用非常相似的结构。 折叠拓扑也类似于 神经生长因子（NGF）和血小板衍生的 生长因子（PDGF），尽管二聚体形成的模式相当复杂。 这三种蛋白质都不同。 2)作为抗体结构基础研究的一部分 特异性，MAB HyHEL-5复合物的晶体结构 与鸡溶菌酶已精制。 此外， 这种抗体与突变溶菌酶的复合物， 约束力已经确定。 在突变体中，存在于 野生型已被赖氨酸（R68 K）取代。 的比较 突变体和野生型已作出，以解释大 这种保守突变对亲和力的影响。