Structural Studies of Inhibin/Activin Receptor Complexes

抑制素/激活素受体复合物的结构研究

• 批准号: 6626183
• 负责人: THOMAS B THOMPSON
• 金额: $ 2.94万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6626183
• 关键词: X ray crystallography; analytical ultracentrifugation; biological signal transduction; cell line; crystallization; gel filtration chromatography; growth factor receptors; hormone receptor; inhibin; inhibitor /antagonist; ligands; postdoctoral investigator; protein folding; protein purification; protein structure; receptor binding; recombinant proteins; structural biology; transfection /expression vector; transforming growth factors

Activin and Inhibin are members of an important superfamily of peptide hormones/growth factors that regulate many cellular growth and differentiation processes. Activin and inhibin play a central role in the reproductive systems of animals by regulation of FSH levels and spermatogenesis. The hormones are also implicated in folliculogenesis. The goal of this research is to better understand the interactions of TGF-beta signaling molecules and their receptors. This proposal focuses on how activin and inhibin interact with the extracellular domains of their signaling receptors RI and RII. Initial goals are to produce significant amounts of protein for use in crystallographic and biophysical studies. Complex formation will be tested and analyzed by gel filtration affinity chromatography, analytical ultracentrifugation, IAsys, and in vitro cellular assays. These methods will be useful in determining how complexes are formed along with their equilibrium and association/ dissociation rate constants. Complexes will be used in crystallization experiments in order to solve their three dimensional structures. Structure determination will be carried out at the Advanced Photon Source at Argonne National Laboratory. These experiments will lead to a better understanding of receptor signaling mechanisms within the TGF-beta superfamily.

激活素和抑制素是调节许多细胞生长和分化过程的重要肽激素/生长因子超家族的成员。激活素和抑制素通过调节 FSH 水平和精子发生在动物生殖系统中发挥核心作用。这些激素还与卵泡发生有关。这项研究的目的是更好地了解 TGF-β 信号分子及其受体的相互作用。该提案重点关注激活素和抑制素如何与其信号受体 RI 和 RII 的胞外结构域相互作用。最初的目标是生产大量蛋白质用于晶体学和生物物理研究。将通过凝胶过滤亲和层析、分析超速离心、IAsys 和体外细胞测定来测试和分析复合物的形成。这些方法将有助于确定复合物的形成方式及其平衡和缔合/解离速率常数。配合物将用于结晶实验，以解析其三维结构。结构测定将在阿贡国家实验室的先进光子源进行。这些实验将有助于更好地了解 TGF-β 超家族内的受体信号传导机制。