Conformational solution studies of the SDS micelle-bound 11-28 fragment of two Alzheimer's beta-amyloid variants (E22K and A21G) using CD, NMR, and MD techniques
2007 (English)In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 87, no 1, 23-39 p.Article in journal (Refereed) Published
The beta-amyloid (A beta) is the major peptide constituent of neuritic plaques in Alzheimer's disease (AD) and its aggregation is believed to play a central role in the pathogenesis of the disease. Naturally occurring mutations resulting in changes in the A beta sequence (pos. 21-23) are associated with familial AD-like diseases with extensive cerebrovascular pathology. It was proved that the mutations alter the aggregation ability of A beta and its neurotoxicity. Among five mutations at positions 21-23 there are two mutations with distinct clinical characteristics and potentially distinct pathogenic mechanism-the Italian (E22K) and the Flemish (A21G) mutations. In our studies we have examined the structures of the 11-28 fragment of the Italian and Flemish AP variants. The fragment was chosen because it been shown to be the most important for amyloid fibril formation detailed structure of both variants A beta(11-28) was determined using CD, 2D NMR, and molecular dynamics techniques under water-SDS micelle conditions. The NMR analysis revealed two distinct sets of proton resonances for the peptides. The studies of both peptides pointed out the existence of well-defined alpha-helical conformation in the Italian mutant, whereas the Flemish was found to be unstructured with the possibility of a bent structure in the central part of the peptide.
Place, publisher, year, edition, pages
2007. Vol. 87, no 1, 23-39 p.
NMR, CD, conformation, Alzheimer's disease, amyloid beta peptide, A beta variants, SDS
IdentifiersURN: urn:nbn:se:su:diva-55899DOI: 10.1002/bip.20768ISI: 000248993000003OAI: oai:DiVA.org:su-55899DiVA: diva2:409555
authorCount :72011-04-082011-03-302011-04-08Bibliographically approved