Details

Autor(en) / Beteiligte

• Jablonowska, Agnieszka
• Bakun, Magdalena
• Kupniewska-Kozak, Anna
• Dadlez, Michal

Titel

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

Ist Teil von

• Journal of molecular biology, 2004-12, Vol.344 (4), p.1037-1049

Ort / Verlag

England

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.