Structural and dynamic views of GM1 ganglioside

Maho Yagi-Utsumi, Koichi Kato

The ganglioside GM1 mediates various physiological and pathological processes mainly through the formation of GM1 clusters on cell surfaces. Therefore, detailed characterization of conformational properties of the glycan moiety of GM1 and the structures and interactions of this glycosphingolipid in membrane environments is necessary for better understanding of the clustering-coupled functional promotion. Nuclear magnetic resonance (NMR) spectroscopy has provided conformational information of GM1 in solution as well as in membrane-like environments. Recently, sophisticated paramagnetism-assisted NMR approaches combined with molecular dynamics simulations have enabled the quantitative exploration of conformational spaces of a series of gangliosides, including GM1, taking into account their minor conformations. NMR techniques have also been successfully applied to investigations of the dynamic interactions of GM1 clusters with amyloidogenic proteins such as amyloid β and α-synuclein associated with neurodegenerative disorders. Further integration of experimental and computational approaches will open up new possibilities to provide structural views of the more complicated heterogeneous systems exemplified by microdomains involving GM1.