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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ando H, Ishida H, Kiso M (2010) Renewed synthetic approach to gangliosides exploiting versatile and powerful synthetic units. Methods Enzymol 478;521–540
Bodner CR, Maltsev AS, Dobson CM, Bax A (2010) Differential phospholipid binding of α-synuclein variants implicated in Parkinson’s disease revealed by solution NMR spectroscopy. Biochemistry 49:862–871
Drickamer K, Taylor ME (1993) Biology of animal lectins. Annu Rev Cell Biol 9:237–264
Ernst B, Magnani JL (2009) From carbohydrate leads to glycomimetic drugs. Nat Rev Drug Discov 8:661–677
Fantini J, Yahi N (2010) Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases. Expert Rev Mol Med 12:e27
Gayen A, Mukhopadhyay C (2008) Evidence for effect of GM1 on opioid peptide conformation: NMR study on leucine enkephalin in ganglioside-containing isotropic phospholipid bicelles. Langmuir 24:5422–5432
Kamiya Y, Yagi-Utsumi M, Yagi H, Kato K (2011a) Structural and molecular basis of carbohydrate-protein interaction systems as potential therapeutic targets. Curr Pharm Des 17:1672–1684
Kamiya Y, Yamamoto S, Chiba Y, Jigami Y, Kato K (2011b) Overexpression of a homogeneous oligosaccharide with 13C labeling by genetically engineered yeast strain. J Biomol NMR 50:397–401
Kamiya Y, Satoh T, Kato K (2012) Molecular and structural basis for N-glycan-dependent determination of glycoprotein fates in cells. Biochim Biophys Acta 1820:1327–1337
Kamiya Y, Yanagi K, Kitajima T, Yamaguchi T, Chiba Y, Kato K (2013) Application of metabolic 13C labeling in conjunction with high-field nuclear magnetic resonance spectroscopy for comparative conformational analysis of high mannose-type oligosaccharides. Biomolecules 3:108–123
Kamiya Y, Satoh T, Kato K (2014) Recent advances in glycoprotein production for structural biology: toward tailored design of glycoforms. Curr Opin Struct Biol 26:44–53
Khatun UL, Mukhopadhyay C (2013) Interaction of bee venom toxin melittin with ganglioside GM1 bicelle. Biophys Chem 180–181:66–75
Lepenies B, Yin J, Seeberger PH (2010) Applications of synthetic carbohydrates to chemical biology. Curr Opin Chem Biol 14:404–411
Luchinat C, Parigi G (2007) Paramagnetic systems in biochemistry: solution NMR studies eMagRes. Wiley, New York
Matsuzaki K, Kato K, Yanagisawa K (2010) Abeta polymerization through interaction with membrane gangliosides. Biochim Biophys Acta 1801:868–877
Nakanishi-Shindo Y, Nakayama K, Tanaka A, Toda Y, Jigami Y (1993) Structure of the N-linked oligosaccharides that show the complete loss of α-1,6-polymannose outer chain from och1, och1mnn1, and och1mnn1alg3 mutants of Saccharomyces cerevisiae. J Biol Chem 268:26338–26345
Peters T, Pinto BM (1996) Structure and dynamics of oligosaccharides: NMR and modeling studies. Curr Opin Struct Biol 6:710–720
Piccinini M, Scandroglio F, Prioni S, Buccinnà B, Loberto N, Aureli M, Chigorno V, Lupino E, Demarco G, Lomartire A, Rinaudo MT, Sonnino S, Prinetti A (2010) Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders. Mol Neurobiol 41:314–340
Satoh T, Suzuki K, Yamaguchi T, Kato K (2014) Structural basis for disparate sugar-binding specificities in the homologous cargo receptors ERGIC-53 and VIP36. PLoS One 9:e87963
Sharon N, Lis H (2003) Lectins, 2nd edn. Springer, Dordrecht
Sugita Y, Okamoto Y (1999) Replica-exchange molecular dynamics method for protein folding. Chem Phys Lett 314:141–151
Takeda Y, Totani K, Matsuo I, Ito Y (2009) Chemical approaches toward understanding glycan-mediated protein quality control. Curr Opin Chem Biol 13:582–591
Ulmer TS, Bax A, Cole NB, Nussbaum RL (2005) Structure and dynamics of micelle-bound human α-synuclein. J Biol Chem 280:9595–9603
Utsumi M, Yamaguchi Y, Sasakawa H, Yamamoto N, Yanagisawa K, Kato K (2009) Up-and-down topological mode of amyloid beta-peptide lying on hydrophilic/hydrophobic interface of ganglioside clusters. Glycoconj J 26:999–1006
Wang Z, Chinoy ZS, Ambre SG, Peng W, Mcbride R, De Vries RP, Glushka J, Paulson JC, Boons GJ (2013) A general strategy for the chemoenzymatic synthesis of asymmetrically branched N-glycans. Science 341:379–383
Wormald MR, Petrescu AJ, Pao YL, Glithero A, Elliott T, Dwek RA (2002) Conformational studies of oligosaccharides and glycopeptides: complementarity of NMR, X-ray crystallography, and molecular modelling. Chem Rev 102:371–386
Yagi-Utsumi M, Kameda T, Yamaguchi Y, Kato K (2010) NMR characterization of the interactions between lyso-GM1 aqueous micelles and amyloid beta. FEBS Lett 584:831–836
Yamaguchi T, Kamiya Y, Choo YM, Yamamoto S, Kato K (2013a) Terminal spin labeling of a high-mannose-type oligosaccharide for quantitative NMR analysis of its dynamic conformation. Chem Lett 42:544–546
Yamaguchi T, Uno T, Uekusa Y, Yagi-Utsumi M, Kato K (2013b) Ganglioside-embedding small bicelles for probing membrane-landing processes of intrinsically disordered proteins. Chem Commun (Camb) 49:1235–1237
Yamaguchi T, Sakae Y, Zhang Y, Yamamoto S, Okamoto Y, Kato K (2014) Exploration of conformational spaces of high-mannose-type oligosaccharides by an NMR-validated simulation. Angew Chem Int Ed Engl in press
Yamamoto S, Yamaguchi T, Erdélyi M, Griesinger C, Kato K (2011) Paramagnetic lanthanide tagging for NMR conformational analyses of N-linked oligosaccharides. Chem Eur J 17:9280–9282
Yamamoto S, Zhang Y, Yamaguchi T, Kameda T, Kato K (2012) Lanthanide-assisted NMR evaluation of a dynamic ensemble of oligosaccharide conformations. Chem Commun (Camb) 48:4752–4754
Zhang Y (2014) Paramagnetism–assisted NMR analyses of conformational dynamics of ganglioside glycans. The Graduate University for Advanced Studies
Zhang Y, Yamamoto S, Yamaguchi T, Kato K (2012) Application of paramagnetic NMR-validated molecular dynamics simulation to the analysis of a conformational ensemble of a branched oligosaccharide. Molecules 17:6658–6671
Zhang Y, Yamaguchi T, Kato K (2013) New NMR tools for characterizing the dynamic conformations and interactions of oligosaccharides. Chem Lett 42:1455–1462
Zhao H, Pan Q, Zhang W, Carmichael I, Serianni AS (2007) DFT and NMR studies of 2JCOH, 3JHCOH, and 3JCCOH spin-couplings in saccharides: C-O torsional bias and H-bonding in aqueous solution. J Org Chem 72:7071–7082
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).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this paper
Cite this paper
Zhang, Y. et al. (2015). Conformational Dynamics of Oligosaccharides Characterized by Paramagnetism-Assisted NMR Spectroscopy in Conjunction with Molecular Dynamics Simulation. In: Chakrabarti, A., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 842. Springer, Cham. https://doi.org/10.1007/978-3-319-11280-0_14
Download citation
DOI: https://doi.org/10.1007/978-3-319-11280-0_14
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-11279-4
Online ISBN: 978-3-319-11280-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)