Structural basis of signal recognition and regulation at the full-length glucagon receptor
作者单位：CAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences
会议名称：《中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议》
会议日期：2018年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学]
关 键 词：GPCR glucagon receptor signaling structural studies
摘 要：The human glucagon receptor(GCGR) belongs to the class B G protein-coupled receptor(GPCR) family and plays a key role in glucose homeostasis and the pathophysiology of type 2 *** we report two crystal structures of full-length GCGR containing both extracellular domain(ECD) and transmembrane domain(TMD) at different conformational ***,the stalk region,which connects the ECD and TMD,and the first extracellular loop(ECL1) undergo major conformational changes in secondary structure during peptide ligand binding,forming key interactions with the ***/deuterium exchange,disulfide cross-linking and molecular dynamics studies suggest that the stalk and ECL1 play critical roles in modulating peptide ligand binding and receptor *** further propose a dual-binding-site trigger model for GCGR activation,which requires conformational changes of the stalk,ECL1 and *** insights into the full-length GCGR structure deepen our understanding about the signaling mechanisms of class B GPCRs.