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Conformational Dynamics of Oligosaccharides Characterized by Paramagnetism-Assisted NMR Spectroscopy in Conjunction with Molecular Dynamics Simulation

  • Ying Zhang
  • Takumi Yamaguchi
  • Tadashi Satoh
  • Maho Yagi-Utsumi
  • Yukiko Kamiya
  • Yoshitake Sakae
  • Yuko Okamoto
  • Koichi Kato
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 842)

Abstract

Oligosaccharides play pivotal roles in physiological and pathological contexts primarily through their interactions with proteins on cell surfaces and in intracellular environments. Although crystallographic approaches provide cumulative information about the atomic details of oligosaccharides complexed with proteins, quantitative characterization of the dynamic conformation of uncomplexed oligosaccharides is essential for better understanding of the energetics of carbohydrate–protein interactions. Nuclear magnetic resonance (NMR) spectroscopy is a potentially powerful tool for describing the conformational dynamics of oligosaccharides in solutions at an atomic resolution. However, methodological improvements are needed in applying NMR techniques to the analyses of the dynamic conformations of oligosaccharides during sample preparation, spectral observation, and data interpretation. This presentation outlines our recently developed method of dealing with dynamic conformational ensembles of oligosaccharides using paramagnetism-assisted NMR spectroscopy in conjunction with molecular dynamics (MD) simulation. A key to this approach is the introduction of a paramagnetic lanthanide ion to the reducing end of oligosaccharides as the source of the atomic long-distance information. We successfully applied this method to the validation of MD-derived conformational spaces occupied by a series of sialyl oligosaccharide moieties of GM1, GM2, and GM3 gangliosides. The applicability of NMR is also revealed for characterizing the dynamic interactions of ganglioside clusters with intrinsically disordered proteins associated with neurodegenerative disorders using ganglioside-embedding small bicelles as nanoscale standardized membrane mimics.

Keywords

Nuclear magnetic resonance Conformational ensemble Paramagnetic effect Molecular dynamics simulation Oligosaccharide Ganglioside Carbohydrate-protein interactions Bicelles 

Notes

Acknowledgements

We wish to acknowledge our former colleagues, Dr. Yoshinori Uekusa, Dr. Kotaro Yanagi, Mr. Tsuyoshi Uno, and Ms. Sayoko Yamamoto, who contributed to the studies reported in this paper. We also thank Dr. Tomoshi Kameda (The National Institute of Advanced Industrial Science and Technology) for useful discussions. Finally, we are grateful to Drs. Yasunori Chiba, Toshihiko Kitajima, and Yoshifumi Jigami (The National Institute of Advanced Industrial Science and Technology) for providing the engineered yeast cells. This work was partly supported by the Okazaki ORION project, the Nanotechnology Platform Program (Molecule and Material Synthesis) of MEXT, Japan, and the JSPS/MEXT Grants in Aid for Scientific Research on Innovation Areas (25102008, 25102009, and 26102518), Scientific Research (A) (24249002), Challenging Exploratory Research (26560451), and Young Scientists (B) (24750170).

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ying Zhang
    • 1
    • 2
    • 3
  • Takumi Yamaguchi
    • 1
    • 2
    • 3
  • Tadashi Satoh
    • 4
    • 3
  • Maho Yagi-Utsumi
    • 1
    • 3
  • Yukiko Kamiya
    • 5
    • 1
  • Yoshitake Sakae
    • 6
  • Yuko Okamoto
    • 6
  • Koichi Kato
    • 1
    • 2
    • 3
    • 7
    • 8
  1. 1.Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural SciencesOkazakiJapan
  2. 2.School of Physical SciencesThe Graduate University for Advanced StudiesOkazakiJapan
  3. 3.Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
  4. 4.JST, PRESTONagoyaJapan
  5. 5.EcoTopia Science Institute and Graduate School of EngineeringNagoya UniversityNagoyaJapan
  6. 6.School of Science, Nagoya UniversityNagoyaJapan
  7. 7.The Glycoscience Institute, Ochanomizu UniversityTokyoJapan
  8. 8.GLYENCE Co., Ltd.NagoyaJapan

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