title: From Compact to String-The Role of Secondary and Tertiary Structure in Charge-Induced Unzipping of Gas-Phase Proteins.
abstract: In the gas phase, protein ions can adopt a broad range of structures, which have been investigated extensively in the past using ion mobility-mass spectrometry (IM-MS)-based methods. Compact ions with low number of charges undergo a Coulomb-driven transition to partially folded species when the charge increases, and finally form extended structures with presumably little or no defined structure when the charge state is high. However, with respect to the secondary structure, IM-MS methods are essentially blind. Infrared (IR) spectroscopy, on the other hand, is sensitive to such structural details and there is increasing evidence that helices as well as β-sheet-like structures can exist in the gas phase, especially for ions in low charge states. Very recently, we showed that also the fully extended form of highly charged protein ions can adopt a distinct type of secondary structure that features a characteristic C5-type hydrogen bond pattern. Here we use a combination of IM-MS and IR spectroscopy to further investigate the influence of the initial, native conformation on the formation of these structures. Our results indicate that when intramolecular Coulomb-repulsion is large enough to overcome the stabilization energies of the genuine secondary structure, all proteins, regardless of their sequence or native conformation, form C5-type hydrogen bond structures. Furthermore, our results suggest that in highly charged proteins the positioning of charges along the sequence is only marginally influenced by the basicity of individual residues. Graphical Abstract ᅟ.
authors.affiliation: Fritz Haber Institute of the Max Planck Society, Faradayweg 4-6, 14195, Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Warnke
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Hoffmann
authors.affiliation: Fritz Haber Institute of the Max Planck Society, Faradayweg 4-6, 14195, Berlin, Germany.
authors.forename: Jongcheol
authors.initials: J
authors.lastname: Seo
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Erwin
authors.initials: E
authors.lastname: De Genst
authors.affiliation: Fritz Haber Institute of the Max Planck Society, Faradayweg 4-6, 14195, Berlin, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: von Helden
authors.affiliation: Fritz Haber Institute of the Max Planck Society, Faradayweg 4-6, 14195, Berlin, Germany. kevin.pagel@fu-berlin.de.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany. kevin.pagel@fu-berlin.de.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pagel
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D006860:Hydrogen Bonding; D000075663:Ion Mobility Spectrometry / Q000379:methods; D007477:Ions / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013055:Spectrophotometry, Infrared / Q000379:methods; D025801:Ubiquitin / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D007477:Ions; D010455:Peptides; D025801:Ubiquitin; D051844:alpha-Synuclein
keywords: Gas-phase proteins; IRMPD spectroscopy; Ion mobility-mass spectrometry; Secondary structure