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A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry

文献类型：期刊论文

作者Qin, Qian1,3; Shi, Xianzhe1; Xu, Guowang1; Wang, Jiayue2,3; Chang, Mengmeng1,3; Wang, Bohong1,3; Xia, Tian1
刊名TALANTA
出版日期2019-03-01
卷号194页码:63-72
关键词Protein-metabolite interactions Metabolomics Native mass spectrometry PPAR gamma protein Lyso-phosphatidylcholine
ISSN号0039-9140
DOI10.1016/j.talanta.2018.10.010
通讯作者Shi, Xianzhe(shixianzhe@dicp.ac.cn) ; Xu, Guowang(xugw@dicp.ac.cn)
英文摘要Protein-metabolite interactions play important roles in many cellular and physiological processes in biological systems. However, the lack of effective research approaches impedes the understanding of the protein-metabolite interactions. In this study, a novel comprehensive strategy by combining metabolomics platform with native mass spectrometry was developed for investigating the protein-metabolite interactions. Peroxisome proliferator-activated receptors gamma (PPAR gamma) is a lipid-binding nuclear receptors that plays a key role in regulating fatty-acid oxidation and lipid metabolism, which was selected as the model protein. Seven metabolites including lyso-phosphatidylcholine (LPC) 16:0, LPC18:0, LPC18:1, arachidonic acid, oleic acid, linoleic acid and palmitoleic acid (p < 0.05) were found to have the possible interactions with the PPAR gamma, these LPCs were discovered as candidate ligands for the first time by using untargeted metabolomics method. Native mass spectrometry based on 15 T Fourier transform ion cyclotron resonance mass spectrometer was employed to directly detect the PPAR gamma-LPCs complexes to obtain their stoichiometry and kinetic constants. Isothermal titration calorimetry, circular dichroism spectrum and molecular modeling were further utilized to investigate the thermodynamics, conformation and binding mechanism of the interaction between PPAR gamma and LPCs. It was found that the PPAR gamma-LPC interaction was an endothermic process, and these LPCs have similar binding constants with stoichiometric number of 1:1. The novel strategy can provide a very useful approach for mapping and identifying unknown protein-metabolite interactions in biological systems.
WOS关键词MOLECULAR INTERACTION ; BINDING ; FLAVONOIDS ; LIGANDS ; MS
资助项目National Natural Science Foundation of China[21575142] ; National Natural Science Foundation of China[21435006]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000456899700009
出版者ELSEVIER SCIENCE BV
资助机构National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
源URL[http://cas-ir.dicp.ac.cn/handle/321008/166160]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Shi, Xianzhe; Xu, Guowang
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Qin, Qian,Shi, Xianzhe,Xu, Guowang,et al. A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry[J]. TALANTA,2019,194:63-72.
APA Qin, Qian.,Shi, Xianzhe.,Xu, Guowang.,Wang, Jiayue.,Chang, Mengmeng.,...&Xia, Tian.(2019).A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry.TALANTA,194,63-72.
MLA Qin, Qian,et al."A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry".TALANTA 194(2019):63-72.

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来源：大连化学物理研究所

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