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Structural and dynamic views of GM1 ganglioside

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Abstract

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.

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Abbreviations

Aβ:

amyloid β-peptide

αSN:

α-synuclein

Chol:

cholesterol

DHPC:

1,2-dihexanoyl-sn-glycero-3-phosphocholine

DMPC:

1,2-dimyristoyl-sn-glycero-3-phosphocholine

DMSO:

determined in dimethyl-d 6 -sulfoxide

DPC:

dodecylphosphocholine

MD:

molecular dynamics

NMR:

nuclear magnetic resonance

NOEs:

nuclear Overhauser effects

PCS:

pseudocontact shift

PRE:

paramagnetic relaxation enhancement

REMD:

replica-exchange molecular dynamics

SM:

sphingomyelin

3D:

three-dimensional

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Acknowledgments

This study was partly supported by a JSPS/MEXT KAKENHI Grant-in-Aid for Scientific Research on Innovation Areas (25102001 and 25102008), Grant-in-Aid for Challenging Exploratory Research (26560451), Research Funding for Longevity Sciences (25–19) from the National Center for Geriatrics and Gerontology, the Nanotechnology Platform Program of MEXT, and the Okazaki ORION project. We thank Drs. Hisashi Okumura, Satoru G. Itoh, and Takumi Yamaguchi for the useful discussion.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan

    Maho Yagi-Utsumi & Koichi Kato

  2. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tababe-dori, Mizuho-ku, Nagoya, 467-8603, Japan

    Maho Yagi-Utsumi & Koichi Kato

  3. The Glycoscience Institute, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan

    Koichi Kato

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  1. Maho Yagi-Utsumi
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Correspondence to Koichi Kato.

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Yagi-Utsumi, M., Kato, K. Structural and dynamic views of GM1 ganglioside. Glycoconj J 32, 105–112 (2015). https://doi.org/10.1007/s10719-015-9587-5

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