DICP OpenIR
A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry
Qin, Qian1,3; Wang, Bohong1,3; Wang, Jiayue2,3; Chang, Mengmeng1,3; Xia, Tian1; Shi, Xianzhe1; Xu, Guowang1
Corresponding AuthorShi, Xianzhe(shixianzhe@dicp.ac.cn) ; Xu, Guowang(xugw@dicp.ac.cn)
KeywordProtein-metabolite interactions Metabolomics Native mass spectrometry PPAR gamma protein Lyso-phosphatidylcholine
Source PublicationTALANTA
2019-03-01
ISSN0039-9140
DOI10.1016/j.talanta.2018.10.010
Volume194Pages:63-72
Funding ProjectNational Natural Science Foundation of China[21575142] ; National Natural Science Foundation of China[21435006]
Funding OrganizationNational 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
WOS SubjectChemistry, Analytical
WOS Research AreaChemistry
WOS KeywordMOLECULAR INTERACTION ; BINDING ; FLAVONOIDS ; LIGANDS ; MS
AbstractProtein-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.
Language英语
Funding OrganizationNational 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
WOS IDWOS:000456899700009
PublisherELSEVIER SCIENCE BV
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166161
Collection中国科学院大连化学物理研究所
Corresponding AuthorShi, Xianzhe; Xu, Guowang
Affiliation1.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
Recommended Citation
GB/T 7714
Qin, Qian,Wang, Bohong,Wang, Jiayue,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.,Wang, Bohong.,Wang, Jiayue.,Chang, Mengmeng.,Xia, Tian.,...&Xu, Guowang.(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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