Functional Analysis of Ligand-Induced Conformational States in Estrogen Receptor

0078143 Myszka，David这项建议的研究旨在更好地了解涉及雌激素受体的配体/受体相互作用如何控制广泛的生物过程。这个项目的前提是，为了获得这些知识，有必要了解与小配体/受体相互作用相关的分子结合事件。结构数据表明，激动剂和拮抗剂配体通过改变雌激素受体的构象状态来改变调节蛋白的雌激素受体结合活性。Biacore是一种表面等离子体共振(SPR)光学生物传感器，被用来直接监测配体/受体复合体的形成动力学，并表征不同配体施加的功能状态。关于配体结合作用的初步动力学数据表明，激动剂和拮抗剂配体通过不同的动力学途径与雌激素受体结合。在这个项目中，这些动力学途径将被量化，这样做将为理解复杂的形成和将结构与功能联系起来提供关键信息。

0078143Myszka, DavidThe research of this proposal is directed at obtaining a better understanding of how ligand/receptor interactions involving estrogen receptors control a wide array of biological processes. This project is based on the premise that to gain this knowledge it is necessary to understand the molecular binding events associated with small ligand/receptor interactions. Structural data suggest that agonist and antagonist ligands alter the estrogen receptor binding activity for regulatory proteins by modifying the conformational state of the receptor. BIACORE, a surface plasmon resonance (SPR) optical biosensor, is being employed to monitor directly the dynamics of ligand/receptor complex formation and to characterize the functional states imposed by different ligands. Preliminary dynamic data on ligand binding interactions demonstrate that agonist and antagonist ligands bind to estrogen receptor via distinct kinetic pathways. In this project, these kinetic pathways will be quantified and by so doing will provide critical information for understanding complex formation and relating structure to function.