title: Alzheimer's disease Abeta peptide fragment 10-30 forms a spectrum of metastable oligomers with marked preference for N to N and C to C monomer termini proximity.
abstract: Oligomers of Abeta peptide have been indicated recently as a possible main causative agent of Alzheimer's disease. However, information concerning their structural properties is very limited. Here Abeta oligomers are studied by non-covalent complexes mass spectrometry and disulfide rearrangement. As a model molecule, an Abeta fragment spanning residues 10-30 (Abeta10-30) has been used. This model peptide is known to contain the core region responsible for Abeta aggregation to fibrils. Non-covalent complexes mass spectrometry indicates that, at neutral pH, monomers are accompanied by oligomers up to hexamers of gradually decreasing population. H-2H exchange studies and direct monomer exchange rate measurements with the use of 15N labeled peptides and mass spectrometry show a fast exchange of monomeric units between oligomers. Disulfide exchange studies of cysteine tagged Abeta10-30 and its mutant show proximity of N-N and C-C termini of monomers in oligomers. The presented data underscore a dynamic character for pre-nucleation forms of Abeta, however, with a marked tendency for parallel strand orientation in oligomers.
authors.affiliation: Department of Biophysics, Institute of Biochemistry and Biophysics, PAS, ul. Pawińskiego 5A, 02-106 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jablonowska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bakun
authors.forename: Anna
authors.initials: A
authors.lastname: Kupniewska-Kozak
authors.forename: Michal
authors.initials: M
authors.lastname: Dadlez
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004220:Disulfides / Q000737:chemistry; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary
chemical_list: D016229:Amyloid beta-Peptides; D004220:Disulfides; D010446:Peptide Fragments