Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine

doi:10.1007/s10858-017-0107-8

	Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine
	Hou, Yaguang1,2,3,7 ; Hu, Wanhui1 ; Li, Xiaona 4; Skinner, John J.1 ; Liu, Dongsheng1 ; Wuthrich, Kurt1,5,6
	2017-05
发表期刊	JOURNAL OF BIOMOLECULAR NMR (IF:2.4[JCR-2023],2.1[5-Year])
ISSN	0925-2738
卷号	68 期号:1 页码:1-6
发表状态	已发表
DOI	10.1007/s10858-017-0107-8
摘要	The amino acid 4-fluoro-l-phenylalanine (4F-Phe) was introduced at the positions of Phe6 and Phe22 in the 29-residue polypeptide hormone glucagon by expressing glucagon in E. coli in the presence of an excess of 4F-Phe. Glucagon regulates blood glucose homeostasis by interaction with the glucagon receptor (GCGR), a class B GPCR. By referencing to the 4F-Phe chemical shifts at varying D2O concentrations, the solvent exposure of the two Phe sites along the glucagon sequence was determined, showing that 4F-Phe6 was fully solvent exposed and 4F-Phe22 was only partially exposed. The incorporation of fluorine atoms in polypeptide hormones paves the way for novel studies of their interactions with membrane-spanning receptors, specifically by differentiating between effects on the solvent accessibility, the line shapes, and the chemical shifts from interactions with lipids, detergents and proteins. Studies of interactions of GCGR with ligands in solution is at this point of keen interest, given that recent crystallographic studies revealed that an apparent small molecule antagonist actually binds as an allosteric effector at a distance of similar to 20 from the orthosteric ligand binding site (Jazayeri et al., in Nature 533:274-277, 2016).
关键词	F-19-NMR Glucagon F-19 chemical shift Solvent exposure from D2O effects
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[31670733]
WOS研究方向	Biochemistry & Molecular Biology ; Spectroscopy
WOS类目	Biochemistry & Molecular Biology ; Spectroscopy
WOS记录号	WOS:000403406900001
出版者	SPRINGER
WOS关键词	PROTEIN-COUPLED RECEPTOR ; CRYSTAL-STRUCTURE ; NMR ; ANTAGONIST ; RESONANCE ; GPCRS ; SITE
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1380
专题	生命科学与技术学院 iHuman研究所_特聘教授组_Kurt Wuthrich组 iHuman研究所_PI研究组_徐菲组生命科学与技术学院_硕士生
通讯作者	Wuthrich, Kurt
作者单位	1.ShanghaiTech Univ, iHuman Inst, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA 6.Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA 7.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China
第一作者单位	iHuman研究所; 生命科学与技术学院
通讯作者单位	iHuman研究所
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Hou, Yaguang,Hu, Wanhui,Li, Xiaona,et al. Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine[J]. JOURNAL OF BIOMOLECULAR NMR,2017,68(1):1-6.
APA	Hou, Yaguang,Hu, Wanhui,Li, Xiaona,Skinner, John J.,Liu, Dongsheng,&Wuthrich, Kurt.(2017).Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine.JOURNAL OF BIOMOLECULAR NMR,68(1),1-6.
MLA	Hou, Yaguang,et al."Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by F-19-NMR observation of 4-fluorophenylalanine".JOURNAL OF BIOMOLECULAR NMR 68.1(2017):1-6.