1. Gas-phase structure of amyloid-β (12-28) peptide investigated by infrared spectroscopy, electron capture dissociation and ion mobility mass spectrometry
- Author
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Charles Desfrançois, Jérôme Lemoine, Fabien Chirot, Guillaume van der Rest, Frédéric Lecomte, Jean-Christophe Poully, Philippe Dugourd, Thi Nga Le, Nicolas Nieuwjaer, Bruno Manil, Gilles Grégoire, Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), ANABIO - ANAlyse BIOmoléculaire RMN et spectrométrie de masse (2011-2013), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CNRS TGE-FTICR, CNRS GDR 3335, Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
ONIOM ,Models, Molecular ,Amyloid peptide ,MOLECULAR-DYNAMICS SIMULATIONS ,Spectrophotometry, Infrared ,Ion-mobility spectrometry ,SECONDARY-STRUCTURE ,Infrared spectroscopy ,Ion Mobility ,PROTEIN ,010402 general chemistry ,Mass spectrometry ,01 natural sciences ,Dissociation (chemistry) ,Mass Spectrometry ,Protein Structure, Secondary ,IR SPECTROSCOPY ,Structural Biology ,Computational chemistry ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,CONFORMATIONAL PREFERENCES ,IRMPD ,TRANSITION MECHANISM ,SPECTRA ,Humans ,ECD ,Infrared multiphoton dissociation ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Conformational isomerism ,Spectroscopy ,Ions ,Quantitative Biology::Biomolecules ,Amyloid beta-Peptides ,Electron-capture dissociation ,Chemistry ,010401 analytical chemistry ,Peptide Fragments ,0104 chemical sciences ,ALZHEIMERS-DISEASE ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,Crystallography ,A-BETA(12-28) ,RANDOM COIL ,Protons ,Gas phase structure - Abstract
International audience; The gas-phase structures of doubly and triply protonated Amyloid-β12-28 peptides have been investigated through the combination of ion mobility (IM), electron capture dissociation (ECD) mass spectrometry, and infrared multi-photon dissociation (IRMPD) spectroscopy together with theoretical modeling. Replica-exchange molecular dynamics simulations were conducted to explore the conformational space of these protonated peptides, from which several classes of structures were found. Among the low-lying conformers, those with predicted diffusion cross-sections consistent with the ion mobility experiment were further selected and their IR spectra simulated using a hybrid quantum mechanical/semiempirical method at the ONIOM DFT/B3LYP/6-31 g(d)/AM1 level. In ECD mass spectrometry, the c/z product ion abundance (PIA) has been analyzed for the two charge states and revealed drastic differences. For the doubly protonated species, N - Cα bond cleavage occurs only on the N and C terminal parts, while a periodic distribution of PIA is clearly observed for the triply charged peptides. These PIA distributions have been rationalized by comparison with the inverse of the distances from the protonated sites to the carbonyl oxygens for the conformations suggested from IR and IM experiments. Structural assignment for the amyloid peptide is then made possible by the combination of these three experimental techniques that provide complementary information on the possible secondary structure adopted by peptides. Although globular conformations are favored for the doubly protonated peptide, incrementing the charge state leads to a conformational transition towards extended structures with 310- and α-helix motifs.
- Published
- 2013
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