Functional Analysis of Ligand-Induced Conformational States in Estrogen Receptor

University Of Utah, Salt Lake City UT

Investigators

Abstract

0078143 Myszka, David The 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.