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Our research focuses on applying state-of-the-art mass spectrometric techniques to the following areas: 1) identification and characterization of protein posttranslational modifications; 2) mapping macromolecular contact surfaces; 3) exploration of the gas-phase fragmentation behavior of various biomolecules following ion-electron interactions; and 4) probing covalent intermediates in the catalysis of non-ribosomal peptide synthetases and polyketide synthases. A major goal is to excel in both analytical technique development and biologically relevant problem solving.
Electron capture dissociation (ECD) can cleave backbone bonds with retention of weakly-bound posttranslational modifications, thereby allowing their localization while simultaneously resulting in amino acid sequence information. By contrast, the main dissociation pathways in slow-heating techniques, such as infrared multiphoton dissociation (IRMPD), are loss of and cleavage within modifications. IRMPD can therefore identify the presence of modifications, and provide complementary structural information compared with ECD. However; one drawback of ECD is that multiply positively charged precursor ions are required, which can pose a challenge for acidic species such as phospho- and sulfopeptides. Alternative negative ion mode activation techniques are therefore of great interest to us, including electron detachment dissociation (EDD) and negative ion ECD (niECD), which was discovered in the Hakansson group. niECD provides identical structural information as conventional ECD but with the added advantage of operating in negative ion mode. In addition, niECD involves charge increase rather than decrease and thus ensures high fragmentation efficiency and improved product ion signal abundance. We incorporate these ion-electron and ion-photon reactions into the field of proteomics to specifically target modified proteins.
The Hakansson group also employs IRMPD for selective dissociation of peptides with chromophores at 943 cm-1, including phosphopeptides, cysteine oxidized peptides, RNA-peptide crosslinks, and phosphopantetheinylated peptides from natural product biosyntehtic enzymes. These experiments are available on both our Fourier transform ion cyclotron resonance (FT-ICR) and Orbitrap Fusion Lumos instruments and allow targeted proteomics of such analytes.
Solution-phase hydrogen/deuterium exchange (HDX) in combination with mass spectrometric detection of proteolytic peptides is a valuable tool for characterization of protein-protein interactions. The exchange rates of amide hydrogens at contact surfaces generally slow down several orders of magnitude compared to hydrogens accessible to the solvent. We utilize the ultrahigh resolution (m/ΔmFWHM of several million) and ppm mass accuracy of FT-ICR mass spectrometry to improve peptide assignment, protein sequence coverage, and mass increase measurements. We recently received new instrumentation that allows coupling of HDX with ion mobility spectrometry and ECD for increased structural resolution.
Finally, we are interested in extending the radical ion chemistry of ECD/niECD and other techniques based on ion-electron interactions (e.g., electron induced dissociation (EID)) to structural characterization of a larger variety of biological molecules, such as oligonucleotides, oligosaccharides, metabolites, and lipids. Fragmentation patterns of both positive and negative ions are investigated, and should provide insights for a deeper understanding of these processes.
Electron capture dissociation (ECD) can cleave backbone bonds with retention of weakly-bound posttranslational modifications, thereby allowing their localization while simultaneously resulting in amino acid sequence information. By contrast, the main dissociation pathways in slow-heating techniques, such as infrared multiphoton dissociation (IRMPD), are loss of and cleavage within modifications. IRMPD can therefore identify the presence of modifications, and provide complementary structural information compared with ECD. However; one drawback of ECD is that multiply positively charged precursor ions are required, which can pose a challenge for acidic species such as phospho- and sulfopeptides. Alternative negative ion mode activation techniques are therefore of great interest to us, including electron detachment dissociation (EDD) and negative ion ECD (niECD), which was discovered in the Hakansson group. niECD provides identical structural information as conventional ECD but with the added advantage of operating in negative ion mode. In addition, niECD involves charge increase rather than decrease and thus ensures high fragmentation efficiency and improved product ion signal abundance. We incorporate these ion-electron and ion-photon reactions into the field of proteomics to specifically target modified proteins.
The Hakansson group also employs IRMPD for selective dissociation of peptides with chromophores at 943 cm-1, including phosphopeptides, cysteine oxidized peptides, RNA-peptide crosslinks, and phosphopantetheinylated peptides from natural product biosyntehtic enzymes. These experiments are available on both our Fourier transform ion cyclotron resonance (FT-ICR) and Orbitrap Fusion Lumos instruments and allow targeted proteomics of such analytes.
Solution-phase hydrogen/deuterium exchange (HDX) in combination with mass spectrometric detection of proteolytic peptides is a valuable tool for characterization of protein-protein interactions. The exchange rates of amide hydrogens at contact surfaces generally slow down several orders of magnitude compared to hydrogens accessible to the solvent. We utilize the ultrahigh resolution (m/ΔmFWHM of several million) and ppm mass accuracy of FT-ICR mass spectrometry to improve peptide assignment, protein sequence coverage, and mass increase measurements. We recently received new instrumentation that allows coupling of HDX with ion mobility spectrometry and ECD for increased structural resolution.
Finally, we are interested in extending the radical ion chemistry of ECD/niECD and other techniques based on ion-electron interactions (e.g., electron induced dissociation (EID)) to structural characterization of a larger variety of biological molecules, such as oligonucleotides, oligosaccharides, metabolites, and lipids. Fragmentation patterns of both positive and negative ions are investigated, and should provide insights for a deeper understanding of these processes.
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Neven N. Mikawy,Carolina Rojas Ramírez,Steven A. DeFiglia, Carson W. Szot, Jessie Le,Carter Lantz,Benqian Wei,Muhammad A. Zenaidee,Greg T. Blakney,Alexey I. Nesvizhskii,Joseph A. Loo,Brandon T. Ruotolo,Jeffrey Shabanowitz,Lissa C. Anderson,Kristina Håkansson
Chunyi Zhao, Nicholas B Borotto,Jennifer Schmidt, Kinshuk Srivastava,Andrew Lowell,Kristina Hakansson,David H Sherman,Brandon T Ruotolo
Journal of the American Society for Mass Spectrometry (2024)
Journal of the American Society for Mass Spectrometryno. 4 (2024): 784-792
Menatallah M. Youssef, Carson W. Szot,Jeff Folz, Luke M. Collier,Hye Kyong Kweon,Steven A. DeFiglia,Miriam F. Ayad,Lobna A. Hussein,Maha F. Abdel-Ghany,Kristina Hakansson
Journal of proteome research (2024)
Analytical chemistryno. 19 (2017): 10188-10193
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#Papers: 119
#Citation: 6734
H-Index: 42
G-Index: 81
Sociability: 6
Diversity: 0
Activity: 0
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