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Molecular Basis of B1-Adrenergic Receptor Function

B1-肾上腺素受体功能的分子基础

基本信息

批准号：
10414984
负责人：
Xin-Yun Huang
金额：
$ 38.14万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10414984
关键词：
Address Adenylate Cyclase Adrenergic Receptor Adrenergic beta-Antagonists Affect American Binding Biochemical Biological Models Biophysics Blood Vessels Cardiac Cardiac Output Catecholamines Cessation of life Chronic Disease Complex Coupling Cryoelectron Microscopy Cyclic AMP Development Disease Electrons Elements Epinephrine Family Future G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Gases Generations Guanine Nucleotide Exchange Factors Guanosine Triphosphate Phosphohydrolases Heart Heart Abnormalities Heart Contractilities Heart Diseases Heart Rate Heart failure Heterotrimeric GTP-Binding Proteins Hormones Human Hypertension Lead Mediating Molecular Molecular Conformation Morbidity - disease rate Movement Myocardial Myocardial Infarction Norepinephrine Nucleotides Pharmacology Phosphotransferases Physiological Process Proteins Public Health Research Project Grants Role Signal Transduction Signaling Protein Specificity Spectrum Analysis Structure System United States base beta-arrestin experimental study extracellular global health heart rhythm inhibitor mortality public health relevance receptor receptor function receptor structure function response side effect stroke risk

项目摘要

Project Description The long-term objective of this research project is to understand the molecular basis of the activation of heterotrimeric G-proteins by b1-adrenergic receptor. Hypertension (high blood pressure) and heart disease are global health concerns. Hypertension can lead to severe complications and increase the risk of stroke and death. Activation of cardiac b1- adrenergic receptor leads to increased heart rate and contractility, thus boosting cardiac output. Mechanistically, following the stimulation of b1-adrenergic receptor, activated G- protein Gs leads to the stimulation of adenylyl cyclase. In this application, we will focus on the structural basis of activation of Gs-protein by b1-adrenergic receptors. We will use biophysical, cellular and pharmacological approaches to gain a deeper understanding of this activation process. We will investigate the conformational changes of G-proteins during their activation by b1-adrenergic receptors. We will examine the coupling specificity of b1-adrenergic receptors and different families of G-proteins. These studies will advance our understanding of the structure and function of b1-adrenergic receptors, and aid future development of new-generations of specific inhibitors of b1-adrenergic receptors with biased signaling and fewer side effects.

项目描述