The studies on the interactions between β2 adrenergic receptor and Gs protein by molecular dynamics simulations

摘要：

　　β2 adrenergic receptor (β2AR) plays important regulatory roles in a variety of cell and organ systems and is an important therapeutic target in the treatment of airway and cardiovascular disease.Recently,crystal structure of β2AR-Gs protein complex was reported,which facilitates the study of the activation mechanism of β2AR and G-protein coupled receptors (GPCRs).In this work,we perform 20-ns molecular dynamics (MD) simulations of β2AR-Gs protein complex with its agonist in explicit lipid and water environment to investigate the activation mechanism of β2AR.We find that,without nanobody stabilizing the complex,the agonist triggers the conformational changes of β2AR sequentially from the extracellular regions to the intracellular regions,especially the intracellular parts of TM3,TM5,TM6,and TM7,which directly interact with Gs protein.Our results show that β2AR-Gs protein complex makes the conformational change in the following sequence:(1) agonist bound part of β2AR,(2) intracellular region of β2AR,and (3) Gs protein.Our results provide the structural basis for the study of the conformational change and activation mechanism of β2AR.

关键词： molecular dynamics β2AR adrenergic receptor GPCRs Gs protein conformational change signal transduction

作者: Zhiwei Feng Tingjun Hou Youyong Li

作者单位: Institute of Functional Nano & Soft Materials(FUNSOM)and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, P.R.China

会议类型: 国际会议

会议名称: The 6th International Conference of Molecular Simulations and Applied Informatics Technologies(第六届国际分子模拟与信息技术应用学术会议(ICMS&I))

会议地点: 南京

会议语种:英文

页码: 539-559

在线出版日期: 2012-05-13（万方平台首次上网日期，不代表论文的发表时间）