Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples.Recently,ion mobility-mass spectrometry(IM-MS)has emerged as a powerful technology for untargeted metabolom...Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples.Recently,ion mobility-mass spectrometry(IM-MS)has emerged as a powerful technology for untargeted metabolomics.The emerging role of IM-MS in untargeted metabolomics enables the separation of metabolite isomers and generation of multidimension data to support the identification of metabolites.In this review,we first introduced the basic principles of IM-MS instruments commonly used for untargeted metabolomics.Then,we demonstrated the application of IM-MS for metabolite separation and identification of both known and unknown metabolites.Finally,we discussed the future developments of IM-MS technology to improve untargeted metabolomics.展开更多
Despite the expansive applications of gas-phase unfolding techniques,the molecular mechanism for the solvent-free forced unfolding pathway which substrate multidomain proteins usually adopt remains elusive at the seco...Despite the expansive applications of gas-phase unfolding techniques,the molecular mechanism for the solvent-free forced unfolding pathway which substrate multidomain proteins usually adopt remains elusive at the secondary structure level.Herein,upon carefully selecting CRM_(197) as a therapeutically-relevant model system containing multiple secondary structure-separated domains,we systematically examine its solvent-free unfolding pathway.Further-more,utilizing the hybrid of noncovalent chemical probing with niacinamide and ion mobility-mass spectrometry-guided all-atom molecular dynamics simulations,we map a nearly complete unfolding atlas for the conjugate vaccine carrier protein CRM_(197) in a domain-and secondary structure-resolved manner.The totality of our data supports the preferential unfolding of the sheet-rich domain,indicating the dynamic transition from β-sheet toα-helix,and demonstrating that helix exhibit comparatively higher stability thanβ-sheets.We propose that this sheet-to-helix dynamic transition may be central to the gas-phase unfolding pathways of multidomain proteins,suggesting the need for systematic studies on additional multidomain protein systems.展开更多
基金The work was supported by National Natural Science Foundation of China(Grant No.31971356)Shang-hai Municipal Science and Technology Major Project(Grant No.2019SHZDZX02)。
文摘Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples.Recently,ion mobility-mass spectrometry(IM-MS)has emerged as a powerful technology for untargeted metabolomics.The emerging role of IM-MS in untargeted metabolomics enables the separation of metabolite isomers and generation of multidimension data to support the identification of metabolites.In this review,we first introduced the basic principles of IM-MS instruments commonly used for untargeted metabolomics.Then,we demonstrated the application of IM-MS for metabolite separation and identification of both known and unknown metabolites.Finally,we discussed the future developments of IM-MS technology to improve untargeted metabolomics.
基金support by the National Key R&D Program of China(No.2022YFA1305200,to GL)National Natural Science Foundation of China(No.22104064 to GL,No.22173020 to JL)the US National Institute of Mental Health(No.R01MH122742,to CJW)for financial and instrumental support.
文摘Despite the expansive applications of gas-phase unfolding techniques,the molecular mechanism for the solvent-free forced unfolding pathway which substrate multidomain proteins usually adopt remains elusive at the secondary structure level.Herein,upon carefully selecting CRM_(197) as a therapeutically-relevant model system containing multiple secondary structure-separated domains,we systematically examine its solvent-free unfolding pathway.Further-more,utilizing the hybrid of noncovalent chemical probing with niacinamide and ion mobility-mass spectrometry-guided all-atom molecular dynamics simulations,we map a nearly complete unfolding atlas for the conjugate vaccine carrier protein CRM_(197) in a domain-and secondary structure-resolved manner.The totality of our data supports the preferential unfolding of the sheet-rich domain,indicating the dynamic transition from β-sheet toα-helix,and demonstrating that helix exhibit comparatively higher stability thanβ-sheets.We propose that this sheet-to-helix dynamic transition may be central to the gas-phase unfolding pathways of multidomain proteins,suggesting the need for systematic studies on additional multidomain protein systems.
