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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.