title: Gas-phase structure of amyloid-β (12-28) peptide investigated by infrared spectroscopy, electron capture dissociation and ion mobility mass spectrometry.
abstract: 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.
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire de Physique des Lasers, CNRS UMR 7538, F-93430, Villetaneuse, France.
authors.forename: Thi Nga
authors.initials: TN
authors.lastname: Le
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Poully
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lecomte
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nieuwjaer
authors.forename: Bruno
authors.initials: B
authors.lastname: Manil
authors.forename: Charles
authors.initials: C
authors.lastname: Desfrançois
authors.forename: Fabien
authors.initials: F
authors.lastname: Chirot
authors.forename: Jerome
authors.initials: J
authors.lastname: Lemoine
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
authors.forename: Guillaume
authors.initials: G
authors.lastname: van der Rest
authors.forename: Gilles
authors.initials: G
authors.lastname: Grégoire
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D007477:Ions / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011522:Protons; D013055:Spectrophotometry, Infrared / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D007477:Ions; D010446:Peptide Fragments; D011522:Protons; C092395:amyloid beta-protein (12-28)
references.citation: Nat Chem. 2009 Jul;1(4):326-31
references.pmid: 20703363
references.citation: J Am Soc Mass Spectrom. 2006 Nov;17(11):1605-1615
references.pmid: 16904337
references.citation: J Am Soc Mass Spectrom. 2004 Dec;15(12):1869-73
references.pmid: 15589763
references.citation: J Mol Graph Model. 2004 Dec;23(3):263-73
references.pmid: 15530822
references.citation: J Am Chem Soc. 2003 Jul 23;125(29):8949-58
references.pmid: 12862492
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12179-84
references.pmid: 12196631
references.citation: Phys Chem Chem Phys. 2005 Apr 7;7(7):1345-8
references.pmid: 19787952
references.citation: Phys Chem Chem Phys. 2009 Jan 7;11(1):125-32
references.pmid: 19081915
references.citation: J Am Chem Soc. 2003 Mar 19;125(11):3353-69
references.pmid: 12630891
references.citation: J Am Soc Mass Spectrom. 2007 Dec;18(12):2146-61
references.pmid: 17951069
references.citation: J Biol Chem. 2009 Feb 20;284(8):4749-53
references.pmid: 18845536
references.citation: J Chem Phys. 2011 Jan 21;134(3):035102
references.pmid: 21261391
references.citation: J Struct Biol. 2000 Jun;130(2-3):153-73
references.pmid: 10940223
references.citation: Phys Chem Chem Phys. 2010 Nov 7;12(41):13448-54
references.pmid: 20838693
references.citation: J Mol Biol. 1992 Jun 20;225(4):1075-93
references.pmid: 1613791
references.citation: Biophys J. 1991 Nov;60(5):1190-201
references.pmid: 1760507
references.citation: Faraday Discuss. 2011;150:243-55; discussion 257-92
references.pmid: 22457952
references.citation: J Am Chem Soc. 2003 May 14;125(19):5954-63
references.pmid: 12733936
references.citation: J Am Chem Soc. 2002 Jun 5;124(22):6407-20
references.pmid: 12033872
references.citation: Mass Spectrom Rev. 2009 May-Jun;28(3):448-67
references.pmid: 19219931
references.citation: J Am Chem Soc. 2005 Feb 23;127(7):2075-84
references.pmid: 15713083
references.citation: J Am Soc Mass Spectrom. 2009 Jun;20(6):1182-92
references.pmid: 19297190
references.citation: J Phys Chem A. 2005 Jan 13;109(1):250-8
references.pmid: 16839114
references.citation: J Phys Chem A. 2009 Jul 16;113(28):8020-6
references.pmid: 19537745
references.citation: J Mol Biol. 1988 May 5;201(1):201-17
references.pmid: 3418697
references.citation: Phys Chem Chem Phys. 2010 Apr 14;12(14):3606-15
references.pmid: 20336259
references.citation: Mass Spectrom Rev. 2009 May-Jun;28(3):468-94
references.pmid: 19241457
references.citation: J Phys Chem B. 2009 Aug 13;113(32):11293-300
references.pmid: 19621911
references.citation: J Am Soc Mass Spectrom. 2002 Mar;13(3):241-9
references.pmid: 11908804
references.citation: J Am Chem Soc. 2004 Feb 25;126(7):1992-2005
references.pmid: 14971932
references.citation: J Am Chem Soc. 2008 Feb 13;130(6):1810-1
references.pmid: 18205355
references.citation: J Phys Chem A. 2010 Jul 1;114(25):6888-96
references.pmid: 20533847
references.citation: J Am Soc Mass Spectrom. 2006 Apr;17(4):576-585
references.pmid: 16503151
references.citation: J Mol Biol. 2006 Sep 22;362(3):567-79
references.pmid: 16930617
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14011-6
references.pmid: 15381764
references.citation: Acc Chem Res. 2006 Sep;39(9):635-45
references.pmid: 16981680
references.citation: J Phys Chem A. 2013 May 16;117(19):3954-9
references.pmid: 23581979
references.citation: Proteins. 2004 Oct 1;57(1):198-204
references.pmid: 15326604
references.citation: J Am Soc Mass Spectrom. 2008 Jun;19(6):780-9
references.pmid: 18400512
references.citation: J Am Soc Mass Spectrom. 2012 Jul;23(7):1173-81
references.pmid: 22528205
references.citation: Structure. 2003 Mar;11(3):295-307
references.pmid: 12623017
references.citation: FEBS J. 2005 Aug;272(15):3938-49
references.pmid: 16045764
references.citation: J Neurochem. 1994 Mar;62(3):1227-30
references.pmid: 8113806
references.citation: Science. 1991 Jul 12;253(5016):179-82
references.pmid: 1853202
references.citation: FEBS Lett. 2003 Dec 4;555(2):371-4
references.pmid: 14644445
references.citation: J Am Chem Soc. 2008 Nov 5;130(44):14640-50
references.pmid: 18844349
references.citation: Phys Chem Chem Phys. 2007 Jun 28;9(24):3082-97
references.pmid: 17612732