Structural and dynamic views of GM1 ganglioside.
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.
Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan.
Maho
M
Yagi-Utsumi
Koichi
K
Kato
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002236:Carbohydrate Conformation; D002462:Cell Membrane / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D051844:alpha-Synuclein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D005677:G(M1) Ganglioside