Structural Studies of Inhibin/Activin Receptor Complexes

激活素和抑制素是一个重要的肽激素/生长因子超家族的成员，调节许多细胞的生长和分化过程。激活素和抑制素通过调节卵泡刺激素水平和精子发生在动物生殖系统中发挥核心作用。这些激素也与卵泡形成有关。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。本研究的重点是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的蛋白质用于晶体学和生物物理学研究。复合物的形成将通过凝胶过滤亲和层析、分析性超离心、IAsys和体外细胞分析进行测试和分析。这些方法将有助于确定配合物是如何形成的，以及它们的平衡和缔合/离解速率常数。配合物将用于结晶实验，以解决其三维结构。结构测定将在阿贡国家实验室的先进光子源上进行。这些实验将有助于更好地理解tgf - β超家族中的受体信号机制。

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.