title: Binding of amyloid beta-peptide to ganglioside micelles is dependent on histidine-13.
abstract: Amyloid beta-peptide (Abeta) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate from regions of neuronal membrane rich in gangliosides. Here we demonstrate using NMR on 15N-labelled Abeta-(1-40) and Abeta-(1-42) that the interaction with ganglioside G(M1) micelles is localized to the N-terminal region of the peptide, particularly residues His13 to Leu17, which become more helical when bound. The key interaction is with His13, which undergoes a G(M1)-specific conformational change. The sialic acid residue of the ganglioside headgroup is important for determining the nature of the conformational change. The isolated pentasaccharide headgroup of G(M1) is not bound, suggesting the need for a polyanionic surface. Binding to heparin confirms this suggestion, since binding is of similar affinity but does not produce the same conformational changes in the peptide. A comparison of Abeta-(1-40) and Abeta-(1-42) indicates that binding to G(M1) micelles is not related to oligomerization, which occurs at the C-terminal end. These results imply that binding to ganglioside micelles causes a transition from random coil to alpha-helix in the N-terminal region, leaving the C-terminal region unstructured.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Williamson
authors.forename: Yu
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Bourne
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Asakura
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D005677:G(M1) Ganglioside / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D008823:Micelles; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D005677:G(M1) Ganglioside; D006639:Histidine