THREE DIMENSIONAL STRUCTURAL ANALYSIS OF THE GONADOTROPINS

促性腺激素的三维结构分析

• 批准号: 5212539
• 负责人: JOYCE LUSTBADER
• 金额: --
• 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/5212539
• 关键词: CHO cells; X ray crystallography; biological signal transduction; carbohydrates; chemical association; chorionic gonadotropin; conformation; crystallization; follicle stimulating hormone; glycoprotein structure; glycosylation; gonadotropins; hormone receptor; luteinizing hormone; molecular site; mutant; nuclear magnetic resonance spectroscopy; polymerase chain reaction; receptor binding; receptor expression

The primary focus of Project II is the analysis of the three-dimensional structure of the gonadotropins. This project collaborates with Project I and III, which supply some of the reagents and techniques to carry out this program. Solutions of the structures of the active and inactive forms of gonadotropins and their receptor interfaces will enable design of hormone agonists and antagonists which will be useful in the control of fertility. It is not possible to design such reagents without solved structures to supply the precise geometry information about the surfaces of the protein. The specific goals of this project are: (1) to determine the structures of the glycosylated biologically active form of hCG and of neuraminidase- treated hCG and to compare the resulting models to our solved structure of HF-treated hCG, an antagonist of hCG; (2) to determine the structure of the hormone receptor interface of hCG and the LH/CG receptor; (3) to determine the structure of FSH; (4) to determine the structure of the subunits of hCG; (5) to design mutants of hCG from its solved structure to produce an hCG antagonist by decreasing the flexibility of hCG; and (6) to continue to develop important novel technology for NMR solutions of three dimensional structures. The project encompasses biophysical methodology (Crystallography & NMR) to achieve these goals.

项目 II 的主要重点是三维空间分析 促性腺激素的结构。 该项目与Project合作 I 和 III，提供了一些试剂和技术来进行 这个程序。活性和非活性结构的解决方案 促性腺激素及其受体界面的形式将使设计成为可能 激素激动剂和拮抗剂，这将有助于控制 的生育能力。 如果没有解决问题，就不可能设计这样的试剂 提供有关表面的精确几何信息的结构 的蛋白质。 本项目的具体目标是：（1）确定结构 hCG 和神经氨酸酶的糖基化生物活性形式- 处理 hCG 并将所得模型与我们解决的结构进行比较 HF处理的hCG，hCG的拮抗剂； (2)确定结构 hCG 和 LH/CG 受体的激素受体界面； (3) 至 确定 FSH 的结构； (4) 确定结构 hCG 亚单位； (5) 从hCG的已解结构中设计突变体 通过降低 hCG 的灵活性来产生 hCG 拮抗剂；和 (6)继续开发NMR解决方案的重要新技术 的三维结构。 该项目涵盖生物物理 方法（晶体学和核磁共振）来实现这些目标。