title: Simultaneous assessment of conformation and aggregation of beta-amyloid peptide using electrospray ionization mass spectrometry.
abstract: Electrospray ionization mass spectrometry was used to study conformation and aggregation of the synthetic beta-amyloid peptide, residues 1-40 (betaA4), as a function of concentration and sample aging. All mass spectra showed a major envelope of peaks corresponding to charge states of 7-3 of the monomeric form of betaA4. In addition, weaker envelopes of peaks corresponding to charge states of dimeric, trimeric, and tetrameric betaA4 species were seen under gentle ionization conditions. The average charge state of the envelope associated with the monomeric form decreased by ca. 0.5 z as samples were aged, indicating that the relatively open form (likely random coil) of the peptide was modified into the more compact form (likely beta-sheet) as a function of sample aging. The aggregate forms became weaker and ultimately were absent both in the more dilute solutions and in aged aliquots of the concentrated sample. These aggregates were interpreted as assemblies of the random coil form. We interpret our inability to see an ion envelope that can be associated with aggregates of the beta-sheet form to be a consequence of the presumed very compact nature of this form. A model for the formation of betaA4 fibrils is proposed and discussed.
authors.affiliation: Laboratory of Cellular and Molecular Biophysics, The National Institute of Child Health and Development, Bethesda, Maryland 20892-1580, USA.
authors.forename: X G
authors.initials: XG
authors.lastname: Chen
authors.forename: S K
authors.initials: SK
authors.lastname: Brining
authors.forename: V Q
authors.initials: VQ
authors.lastname: Nguyen
authors.forename: A L
authors.initials: AL
authors.lastname: Yergey
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D046911:Macromolecular Substances; D013058:Mass Spectrometry / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D046911:Macromolecular Substances; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)