HCG-LH/CG 受体结合和激活-猫眼课题宝

HCG-LH/CG 受体结合和激活

批准号：

7222641

负责人：

J DAVID PUETT

金额：

$47.3万

依托单位：

UNIVERSITY OF GEORGIA

依托单位国家：

美国

项目类别：

财政年份：

1983

资助国家：

美国

项目状态：

已结题

起止时间：

1983-09-01 至 2010-04-30

来源：

https://reporter.nih.gov/project-details/7222641

关键词：

Address Affinity Agonist Architecture Binding Biological C-terminal Cell membrane Cells Chorionic Gonadotropin Class Compatible Complex Coupling Development Disease Engineering Epitopes Equilibrium Face Family Female Future G-Protein-Coupled Receptors GTP-Binding Proteins Glycoproteins Goals Gonadotropins Helix (Snails)Homology Modeling Hormone Receptor Hormones Human Human Engineering Investigation LH Receptors Laboratory Research Lead Leucine-Rich Repeat Ligand Binding Ligands Luteinizing Hormone Mediating Methodology Modeling Molecular Molecular Conformation Mutation Nature Numbers Orphan Ovarian Hyperstimulation Syndrome Precocious Puberty Process Property Protein Engineering Qualifying Range Reagent Receptor Activation Reproductive Endocrinology Research Rhodopsin Series Shapes Signal Pathway Signal Transduction Site Solutions Structure Structure-Activity Relationship Techniques Testing analog base concept design ear helix extracellular inhibitor/antagonist male member mimetics mutant receptor receptor binding receptor structure function reproductive response small molecule success

项目摘要

项目成果

J DAVID PUETT的其他基金

相似基金

相关文献

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

DESCRIPTION (provided by applicant): The long-range goals of this project are delineation, at the molecular level, of: (a) the structural determinants responsible for specific, high-affinity binding of the heterodimeric glycoprotein hormone, human choriogonadotroin (hCG), to the lutropin/choriogonadotropin receptor (LHR), a member of the G protein-coupled receptor superfamily; (b) the mechanisms of ligand-dependent and ligand-independent LH receptor activation; and (c) the mechanism by which the receptor activates Gs to initiate intracellular signaling pathways. Several recent advances offer promise that elucidation of these fundamental issues in reproductive endocrinology are realistically achievable. Two specific aims, based upon emerging concepts of conformational plasticities of both the hormone and receptor, are proposed for this project. 1. Delineation of hCG and LHR binding determinants: This aim represents a continuation of ongoing studies to elucidate structures of and contact sites between wild type and engineered analogs of hCG and the receptor ectodomain, with a rigorous test of the proposed model of the ectodomain that is postulated to have a cusp shape due to a series of leucine-rich repeats. 2. Mechanisms of receptor activation and Gs coupling: This aim addresses the mechanisms by which wild type and engineered extracellular hCG-ectodomain complexes activate the transmembrane portion of the receptor, the resulting structural changes of the transmembrane helices and intracellular loops responsible for LHR activation, and elucidation of determinants in LHR required for Gs activation. A combination of protein engineering, biophysical investigations, and cell/molecular biological techniques will be utilized to address these aims. Success of this project will greatly enhance our understanding of fundamental mechanisms in male and female reproductive endocrinology and provide new information to assist rational design of LHR agonists and antagonists.

期刊论文(74)

专著(0)

科研奖励(0)

会议论文