title: The Arctic mutation alters helix length and type in the 11-28 beta-amyloid peptide monomer-CD, NMR and MD studies in an SDS micelle.
abstract: The beta-amyloid (Abeta) is the major peptide constituent of neuritic plaques in Alzheimer's disease, and its aggregation is believed to play a central role in the pathogenesis of the disease. Naturally occurring mutations resulting in changes in the Abeta sequence (pos. 21-23) are associated with familial Alzheimer's-like diseases with extensive cerebrovascular pathology. It has been demonstrated that such mutations alter the aggregation ability of Abeta and its neurotoxicity. Among the five mutations at positions 21-23 there is one with distinct clinical characteristics and a potentially distinct pathogenic mechanism-the Arctic (E22G) mutation. We have examined the structures of fragment 11-28 of the native peptide and its E22G variant. This fragment was chosen because it has been shown to be a good model for conformational and aggregation studies as it contains the hydrophobic core responsible for aggregation and the residues critical to alpha-secretase cleavage of APP. The detailed structure of the two peptides was determined using CD, 2D NMR and molecular dynamics techniques under water-SDS micelle conditions. Our studies indicated the existence of partially alpha- and 3(10)-helical conformations in the native and mutated peptide, respectively.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Pomorskie, Poland. sylwia@chem.univ.gda.pl
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
authors.forename: Paulina
authors.initials: P
authors.lastname: Czaplewska
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikorska
authors.forename: Marta
authors.initials: M
authors.lastname: Spodzieja
authors.forename: Aleksandra S
authors.initials: AS
authors.lastname: Kołodziejczyk