Mechanochemical Activation of Class-B G-Protein-Coupled Receptor upon Peptide-Ligand Binding

doi:10.1021/acs.nanolett.0c02333

	Mechanochemical Activation of Class-B G-Protein-Coupled Receptor upon Peptide-Ligand Binding
	Lo Giudice, Cristina 2; Zhang, Haonan 1; Wu, Beili 1; Alsteens, David 2
刊名	NANO LETTERS
	2020-07-08
卷号	20 期号:7 页码:5575-5582
关键词	Atomic force microscopy single-molecule force spectroscopy human glucagon receptor G-protein-coupled receptors mechanotransduction
ISSN号	1530-6984
DOI	10.1021/acs.nanolett.0c02333
通讯作者	Alsteens, David(david.alsteens@uclouvain.be)
英文摘要	Glucagon binding to the class-B G-protein-coupled glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting. Recently, GCGR crystal structures have highlighted the conformation and molecular details of inactive and active receptor states. However, the dynamics of the conformational changes accompanying GCGR activation remains unclear. Here, we use multiplex force-distance curve-based atomic force microscopy (FD-based AFM) to probe in situ glucagon binding to individual GCGRs and monitor dynamically the transition to the active conformer. After a "dock" step, in which glucagon is partially bound to the GCGR extracellular domain, further interactions of the N-terminus with the transmembrane domain trigger an increase in the stiffness of the complex, adopting a highly stable and rigid "lock" conformer. This mechanotransduction is key for G-protein recruitment.
资助项目	Universite' Catholique de Louvain ; Fonds National de la Recherche Scientifique (F.R.S.-FNRS)[PDR T.0090.15] ; European Molecular Biology Organization (EMBO)[ALTF 542-2018]
WOS关键词	GLUCAGON RECEPTOR ; INSIGHTS ; COMPLEX
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000548893200115
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292088]
专题	中国科学院上海药物研究所
通讯作者	Alsteens, David
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 2.Catholic Univ Louvain, Louvain Inst Biomol Sci & Technol, Louvain La Neuve, Belgium
推荐引用方式 GB/T 7714	Lo Giudice, Cristina,Zhang, Haonan,Wu, Beili,et al. Mechanochemical Activation of Class-B G-Protein-Coupled Receptor upon Peptide-Ligand Binding[J]. NANO LETTERS,2020,20(7):5575-5582.
APA	Lo Giudice, Cristina,Zhang, Haonan,Wu, Beili,&Alsteens, David.(2020).Mechanochemical Activation of Class-B G-Protein-Coupled Receptor upon Peptide-Ligand Binding.NANO LETTERS,20(7),5575-5582.
MLA	Lo Giudice, Cristina,et al."Mechanochemical Activation of Class-B G-Protein-Coupled Receptor upon Peptide-Ligand Binding".NANO LETTERS 20.7(2020):5575-5582.