title: Up-and-down topological mode of amyloid beta-peptide lying on hydrophilic/hydrophobic interface of ganglioside clusters.
abstract: Growing evidence has indicated that GM1 ganglioside specifically interacts with Amyloid beta-peptide (Abeta) and thereby promotes Alzheimer's disease-associated Abeta assembly. To characterize the conformation of Abeta bound to the ganglioside, we performed 920 MHz ultra-high field NMR analyses using isotopically labeled Abeta(1-40) in association with GM1 and lyso-GM1 micelles. Our NMR data revealed that (1) Abeta(1-40) forms discontinuous alpha-helices at the segments His(14)-Val(24) and Ile(31)-Val(36) upon binding to the gangliosidic micelles, leaving the remaining regions disordered, and (2) Abeta(1-40) lies on hydrophobic/hydrophilic interface of the ganglioside cluster exhibiting an up-and-down topological mode in which the two alpha-helices and the C-terminal dipeptide segment are in contact with the hydrophobic interior, whereas the remaining regions are exposed to the aqueous environment. These findings suggest that the ganglioside clusters serve as a unique platform for binding coupled with conformational transition of Abeta molecules, rendering their spatial rearrangements restricted to promote specific intermolecular interactions.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Utsumi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sasakawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D005732:Gangliosides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D005732:Gangliosides; D008823:Micelles