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.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Glycosphingolipids were initially discovered by Thudichum who identified sphingosine as their primary part and named it after the mythological riddle of Sphinx because of its enigmatic nature [1]. At present, it is widely known that glycosphingolipids, including gangliosides, play physiological and pathological roles in animal cells as receptors for microbial toxins, mediators of cell adhesion, and modulators of signal transduction [2]. GM1, a ganglioside abundant in neuronal membranes, is one of the most extensively studied glycosphingolipids (Fig. 1a). This glycolipid serves as a target of growth-regulatory galectin-1 [3], the nerve growth factor receptor Trk [4], cholera toxin [5], and auto-antibodies that are associated with Guillain–Barré syndrome [6]. The various functions of gangliosides in physiological and pathological contexts are thought to be based on their assembling properties on cell surfaces. Recently, growing evidence has indicated that GM1 clusters on neuronal cell surfaces offer unique platforms for binding coupled with the conformational transition of amyloidogenic proteins involved in neurodegenerative diseases, e.g., amyloid β (Aβ) in Alzheimer’s disease [7, 8]. Therefore, GM1 can be a potential therapeutic target for various intractable diseases. For better understanding of the mechanisms underlying such a clustering-coupled functional promotion, it is highly desirable to obtain detailed conformational information of the carbohydrate moieties of this molecule and to provide in-depth descriptions of the structures and interactions of gangliosides on membranes.
Recently, sophisticated nuclear magnetic resonance (NMR) techniques typified by paramagnetism-assisted approaches along with computational methods have successfully provided structural information of gangliosides, including GM1, in solution as well as in membrane-like environments. This article outlines the cutting-edge views of conformations and interactions of GM1 ganglioside, highlighting its dynamic properties.
Dynamic structure of GM1 glycan
The conformations of several gangliosides have been traditionally characterized by NMR spectroscopy, primarily on the basis of nuclear Overhauser effects (NOEs) observed between sugar residues of the liberated pentasaccharides [9–11] as well as the entire molecules in aqueous micelles [12, 13] and organic solvents [14, 15]. The overall conformations of the GM1 glycan determined to date by inspecting the NMR data have been quite consistent with each other, except for that determined in dimethyl-d6-sulfoxide (DMSO). Namely, the core -GalNAcIII-(NeuAc)-GalII- part exhibits a well-defined bouquet-like structure by the interaction of NeuAc with the GalNAcIII residue. This structure is consistent with the solvent accessibility of the amide groups of the sugar residues estimated by the inspection of the water saturation effects, indicating that the amide group of NeuAc is more exposed to the aqueous environment than the amide group of GalNAcIII [13].
On the other hand, crystallographic studies have visualized three-dimensional (3D) structures of the GM1 pentasaccharide recognized by cholera toxin, AB5 toxin, and polyoma virus [5, 16, 17]. In these structures, the outer branch of the carbohydrate chain is involved in the interactions with these hazardous binders. The pentasaccharide conformations differ among these complexes and are deviated from the NOE-derived NMR structures, suggesting that GM1 glycan undergoes conformational alteration upon binding to proteins in a ligand-dependent manner.
Recently, a paramagnetism-assisted NMR technique has been developed for the conformational characterization of oligosaccharides in solution. This technique exploits paramagnetic probes such as lanthanide tags and spin labels attached to the reducing end of the oligosaccharide, which can induce paramagnetic effects such as pseudocontact shift (PCS) and paramagnetic relaxation enhancement (PRE) as NOE-independent sources of long-distance information [18–22]. In general, NMR data of flexible oligosaccharides should be interpreted as the population-weighted average derived from a dynamic conformational ensemble rather than a limited number of conformational states. Therefore, the paramagnetic NMR data were used for experimental validation of a conformational space proposed by theoretical approaches. A PCS-based NMR experiment in conjunction with molecular dynamics (MD) simulation was applied to conformational characterization of a series of ganglioside oligosaccharides, including the GM1 pentasaccharide [23–25]. Considerably long calculation times were necessary for exploration of the conformational spaces of these oligosaccharides by MD simulation with explicit water molecules. For example, replica-exchange MD (REMD) simulation was employed to obtain experimentally validated torsion angle density maps of the GM1 pentasaccharide [25]. Figure 1b compares the PCS-validated conformational spaces of oligosaccharides derived from three gangliosides, GM1, GM2, and GM3, indicating similarities between the GM1 pentasaccharide and the GM2 tetrasaccharide in terms of the conformational spaces of their common parts, i.e., the GalII-GlcI, NeuAc-GalII, and GalNAcIII-GalII glycosidic linkage conformations. In contrast, the GM3 trisaccharide exhibits a distinct conformational ensemble regarding the NeuAc-GalII glycosidic linkage. In the GM3 trisaccharide, the linkage conformation is most highly populated in the cluster (ϕ, ψ) = (45 ± 11, −177 ± 11°), whereas the corresponding conformational cluster is missing for the sialyl linkage of the GM1 and GM2 oligosaccharides. These data indicate that the GalNAcIII residue restricts the conformational freedom of the NeuAc-GalII glycosidic linkage in these branched glycans, whereas the outermost GalIV residue has no significant impact on the conformation of the remaining parts of the carbohydrate moiety in GM1.
Although the experimentally validated conformational landscape is qualitatively consistent with the previously reported φ-ψ maps regarding the major conformations, which correspond to the previously reported NOE-based structures, it offers more quantitative views of the individual conformer populations, including those of the minor conformers (Fig. 1b). The ligand-bound conformers of the GM1 pentasaccharide observed in crystal structures were all identified in the conformational ensemble thus obtained, suggesting that the specific conformations are selected from the dynamic ensemble upon binding (Fig. 1c and d).
Structures and interactions of GM1 in membrane environments
NMR spectroscopy is potentially useful for the characterization of the structure and dynamics of the glycolipid assemblies if one could design and create appropriate membrane mimics suitable for sophisticated high-resolution spectral measurements. NMR studies indicated that the glycan conformation of GM1 displayed on its aqueous micelles is almost identical to that of the liberated pentasaccharide [12, 13]. Possible effects of the phospholipid membrane surface on the conformation of gangliosides embedded therein were examined by NMR spectroscopy using small mixed micelles composed of dodecylphosphocholine (DPC) and GM1 in aqueous solution [10, 26]. The results showed that the glycosidic linkage conformations of GalII-GlcI and GalIV-GalNAcIII are significantly altered in DPC micelles. MD simulation indicated that conformations of the GalII-GlcI and GalIV-GalNAcIII linkages are restricted in a dipalmitoylphosphatidylcholine bilayer, leaving the GlcI residue fully extended away from the bilayer surface [27].
In addition, the conformation of GM1 embedded in membrane-mimicking phospholipid bicelles was studied by paramagnetism-assisted NMR experiments in conjunction with MD simulations [28]. In this study, PREs were measured for the membrane-embedded GM1 molecules employing both water-soluble and membrane-anchored paramagnetic probes. MD simulations based on the PRE data revealed that in GM1 in the membrane environment, the GalIV and NeuAc residues have higher flexibility than the other portions of the glycan. In addition, these two residues exhibited larger PRE effects by the water-soluble paramagnetic probe, indicating that they were most accessible in the membrane-embedded form of GM1, consistent with their involvement in interactions with the toxins and viruses as the primary acceptor sites.
A series of NMR studies have characterized the interactions of GM1 clusters with Aβ using aqueous micelles composed of GM1 or lyso-GM1 [13, 29, 30]. The PRE and chemical shift perturbation data underscore the importance of the sugar–lipid interface of the ganglioside clusters for accommodating Aβ [13]. The chemical shift titration and transverse relaxation-optimized spectroscopy-based saturation transfer data have indicated that the interaction between Aβ and the GM1 micelles involves multiple steps, including the initial encounter complex formation and the accommodation process for the two α-helices and the C-terminal Val39–Val40 dipeptide segment in the hydrophobic interior [29] (Fig. 2a). It was further demonstrated that Aβ exhibits a β-structure at higher densities on the GM1 micelles [30]. These findings suggest that the ganglioside clusters offer a unique platform at their hydrophobic/hydrophilic interface for binding coupled with α-helix formation of Aβ molecules, thereby restricting their spatial rearrangements to promote specific intermolecular interactions depending on the Aβ density on the gangliosidic clusters (Fig. 2b).
Recently, small ganglioside-embedding bicelles have been proposed as standardized nanoscale membrane models for detailed NMR analyses of the interactions between ganglioside clusters and biomolecules, including neuropeptides such as substance P and bradykinin, as well as intrinsically disordered proteins associated with neurodegenerative diseases [31–33]. Khatun et al. have shown that intrinsically unstructured neuropeptides strongly bound lipid bilayers and thereby attained a well-ordered secondary structure on the membrane containing GM1 or other gangliosides [32]. Moreover, experiments on ganglioside-containing bicelles have successfully demonstrated that α-synuclein (αSN) is capable of interacting with GM1 and GM2 but not GM3 through its interaction hot spots located in the N-terminal segment [33] (Fig. 2c). In larger anionic membranes, this protein forms long α-helical segments that cannot be accommodated in the limited sizes of the bicelles [34–37]. These data highlight the utility of the small ganglioside-embedding bicelles for the characterization of the initial encounter complex formation of ganglioside clusters with their cognate proteins depending on their outer carbohydrate structures.
GM1 in microdomains: future issues
Accumulating evidence has indicated that gangliosides can form certain ordered phases known as microdomains in the presence of phospholipids, sphingomyelin (SM), and cholesterol (Chol). In particular, various physicochemical methods, including atomic force microscopy [38], Fӧrester resonance energy transfer [39], and imaging mass spectrometry [40], have demonstrated the Chol-dependent cohesive phase separation of GM1 and the preferential colocalization of GM1 with Chol on lipid surfaces.
Recent studies have underscored the important physiological and pathological roles of the microdomains involving GM1 gangliosides in both physiological and pathological states [41]. Namely, GM1 microdomains mediate cell signaling and immune responses and are also involved in the onset and development of cancers and neurodegenerative diseases caused by the pathological protein aggregation of Aβ [38, 42–44], αSN [45], and prion proteins [46]. Therefore, atomic information regarding GM1 clustering depending on SM and Chol is crucial for further understanding of the mechanisms underlying disease progression.
MD simulations have shown that GM1 cluster formation is specifically induced in GM1/SM/Chol membranes, in which Chol critically suppresses membrane fluidity, establishing a hydrogen bond between the OH group of Chol and the oxygen atom at the GlcI-sphingosine junction and keeping the sphingolipid moieties of GM1 molecules close to each other to facilitate cluster formation [44, 47]. However, the atomic-level experimental characterization of carbohydrate–carbohydrate and carbohydrate–protein interactions involving ganglioside clusters on microdomains remains largely unexplored. This is primarily because the experimental methodology has been undeveloped for such complicated heterogeneous systems composed of proteins, carbohydrates, as well as lipids. In addition, the altered acyl chain length of glycosphingolipid can affect the molecular assembly state and subsequent biological events [48–50]. To observe such enigmatic targets, it is obviously necessary to develop multilateral experimental approaches, including stable isotope-assisted solid-state NMR spectroscopy, using appropriately designed model systems [51]. The integration of biophysics-based experimental observations and theoretical approaches will be the key for answering the remaining Sphinx’s riddle.
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
References
Thudichum, J.L.W.: A treatise on the chemical constitution of the brain. Baillière, Tindall & Cox, London (1884)
Regina Todeschini, A., Hakomori, S.I.: Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim Biophys Acta 1780(3), 421–433 (2008)
Kopitz, J., von Reitzenstein, C., Burchert, M., Cantz, M., Gabius, H.J.: Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture. J Biol Chem 273(18), 11205–11211 (1998)
Ichikawa, N., Iwabuchi, K., Kurihara, H., Ishii, K., Kobayashi, T., Sasaki, T., Hattori, N., Mizuno, Y., Hozumi, K., Yamada, Y., Arikawa-Hirasawa, E.: Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth. J Cell Sci 122(Pt 2), 289–299 (2009). doi:10.1242/jcs.030338
Holmgren, J., Lonnroth, I., Mansson, J., Svennerholm, L.: Interaction of cholera toxin and membrane GM1 ganglioside of small intestine. Proc Natl Acad Sci U S A 72(7), 2520–2524 (1975)
Yuki, N.: Carbohydrate mimicry: a new paradigm of autoimmune diseases. Curr Opin Immunol 17(6), 577–582 (2005)
Matsuzaki, K., Kato, K., Yanagisawa, K.: Ab polymerization through interaction with membrane gangliosides. Biochim Biophys Acta 1801(8), 868–877 (2010). doi:10.1016/j.bbalip.2010.01.008
Ariga, T., McDonald, M.P., Yu, R.K.: Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease–a review. J Lipid Res 49(6), 1157–1175 (2008)
Scarsdale, J.N., Prestegard, J.H., Yu, R.K.: NMR and computational studies of interactions between remote residues in gangliosides. Biochemistry 29(42), 9843–9855 (1990)
Acquotti, D., Poppe, L., Dabrowski, J., Wilhelm Von der Lieth, C., Sonnino, S., Tettamanti, G.: Three-dimensional structure of the oligosaccharide chain of GM1 ganglioside revealed by a distance-mapping procedure: a rotating and laboratory frame nuclear overhauser enhancement investigation of native glycolipid in dimethyl sulfoxide and in water-dodecylphosphocholine solutions. J Am Chem Soc 112(21), 7772–7778 (1990)
Brocca, P., Bernardi, A., Raimondi, L., Sonnino, S.: Modeling ganglioside headgroups by conformational analysis and molecular dynamics. Glycoconj J 17(5), 283–299 (2000)
Brocca, P., Berthault, P., Sonnino, S.: Conformation of the oligosaccharide chain of GM1 ganglioside in a carbohydrate-enriched surface. Biophys J 74(1), 309–318 (1998)
Yagi-Utsumi, M., Kameda, T., Yamaguchi, Y., Kato, K.: NMR characterization of the interactions between lyso-GM1 aqueous micelles and amyloid b. FEBS Lett 584(4), 831–836 (2010)
Sillerud, L.O., Yu, R.K., Schafer, D.E.: Assignment of the carbon-13 nuclear magnetic resonance spectra of gangliosides GM4, GM3, GM2, GM1, GD1a, GD1b, and GT1b. Biochemistry 21(6), 1260–1271 (1982)
Koerner Jr., T.A., Prestegard, J.H., Demou, P.C., Yu, R.K.: High-resolution proton NMR studies of gangliosides. 1. Use of homonuclear two-dimensional spin-echo J-correlated spectroscopy for determination of residue composition and anomeric configurations. Biochemistry 22(11), 2676–2687 (1983)
Neu, U., Woellner, K., Gauglitz, G., Stehle, T.: Structural basis of GM1 ganglioside recognition by simian virus 40. Proc Natl Acad Sci U S A 105(13), 5219–5224 (2008)
Ng, N.M., Littler, D.R., Paton, A.W., Le Nours, J., Rossjohn, J., Paton, J.C., Beddoe, T.: EcxAB is a founding member of a new family of metalloprotease AB5 toxins with a hybrid cholera-like B subunit. Structure 21(11), 2003–2013 (2013). doi:10.1016/j.str.2013.08.024
Zhang, Y., Yamaguchi, T., Kato, K.: New NMR tools for characterizing the fynamic conformations and interacctions of oligosaccharides. Chem Lett 42(12), 1455–1462 (2013)
Yamaguchi, Y., Yamaguchi, T., Kato, K.: Structural analysis of oligosaccharides and glycoconjugates using NMR. Adv Neurobiol 9, 165–183 (2014). doi:10.1007/978-1-4939-1154-7_8
Yamaguchi, T., Kato, K.: Paramagnetism-assisted nuclear magnetic resonance analysis of dynamic conformations and interactions of oligosaccharides. Glycosci Biol Med 1, 137–145 (2014). doi:10.1007/978-4-431-54841-6_101
Erdélyi, M., d’Auvergne, E., Navarro-Vázquez, A., Leonov, A., Griesinger, C.: Dynamics of the glycosidic bond: conformational space of lactose. Chemistry 17(34), 9368–9376 (2011). doi:10.1002/chem.201100854
Canales, A., Mallagaray, A., Pérez-Castells, J., Boos, I., Unverzagt, C., André, S., Gabius, H.J., Cañada, F.J., Jiménez-Barbero, J.: Breaking pseudo-symmetry in multiantennary complex N-glycans using lanthanide-binding tags and NMR pseudo-contact shifts. Angew Chem Int Ed Engl 52(51), 13789–13793 (2013). doi:10.1002/anie.201307845
Yamamoto, S., Zhang, Y., Yamaguchi, T., Kameda, T., Kato, K.: Lanthanide-assisted NMR evaluation of a dynamic ensemble of oligosaccharide conformations. Chem Commun (Camb) 48(39), 4752–4754 (2012). doi:10.1039/c2cc30353a
Zhang, Y., Yamamoto, S., Yamaguchi, T., Kato, K.: Application of paramagnetic NMR-validated molecular dynamics simulation to the analysis of a conformational ensemble of a branched oligosaccharide. Molecules 17(6), 6658–6671 (2012). doi:10.3390/molecules17066658
Zhang, Y., Yamaguchi, T., Satoh, T., Yagi-Utsumi, M., Kamiya, Y., Sakae, Y., Okamoto, Y., Kato, K.: Conformational dynamics of oligosaccharides characterized by paramagnetism-assisted NMR spectroscopy in conjunction with molecular dynamics simulation. Adv Exp Med Biol 842, 217–230 (2015). doi:10.1007/978-3-319-11280-0_14
Poppe, L., van Halbeek, H., Acquotti, D., Sonnino, S.: Carbohydrate dynamics at a micellar surface: GD1a headgroup transformations revealed by NMR spectroscopy. Biophys J 66(5), 1642–1652 (1994). doi:10.1016/S0006-3495(94)80956-7
Patel, R.Y., Balaji, P.V.: Characterization of the conformational and orientational dynamics of ganglioside GM1 in a dipalmitoylphosphatidylcholine bilayer by molecular dynamics simulations. Biochim Biophys Acta 1768(6), 1628–1640 (2007). doi:10.1016/j.bbamem.2007.02.020
Demarco, M.L., Woods, R.J., Prestegard, J.H., Tian, F.: Presentation of membrane-anchored glycosphingolipids determined from molecular dynamics simulations and NMR paramagnetic relaxation rate enhancement. J Am Chem Soc 132(4), 1334–1338 (2010). doi:10.1021/ja907518x
Utsumi, M., Yamaguchi, Y., Sasakawa, H., Yamamoto, N., Yanagisawa, K., Kato, K.: Up-and-down topological mode of amyloid β-peptide lying on hydrophilic/hydrophobic interface of ganglioside clusters. Glycoconj J 26(8), 999–1006 (2009). doi:10.1007/s10719-008-9216-7
Yagi-Utsumi, M., Matsuo, K., Yanagisawa, K., Gekko, K., Kato, K.: Spectroscopic characterization of intermolecular interaction of amyloid β promoted on GM1 micelles. Int J Alzheimers Dis 2011, 925073 (2010). doi:10.4061/2011/925073
Khatun, U.L., Goswami, S.K., Mukhopadhyay, C.: Modulation of the neurotensin solution structure in the presence of ganglioside GM1 bicelle. Biophys Chem 168–169, 48–59 (2012). doi:10.1016/j.bpc.2012.06.003
Khatun, U.L., Gayen, A., Mukhopadhyay, C.: Capability of ganglioside GM1 in modulating interactions, structure, location and dynamics of peptides/proteins: biophysical approaches: interaction of ganglioside GM1 with peptides/proteins. Glycoconj J 31(6–7), 435–447 (2014). doi:10.1007/s10719-014-9554-6
Yamaguchi, T., Uno, T., Uekusa, Y., Yagi-Utsumi, M., Kato, K.: Ganglioside-embedding small bicelles for probing membrane-landing processes of intrinsically disordered proteins. Chem Commun (Camb) 49(12), 1235–1237 (2013). doi:10.1039/c2cc38016a
Ulmer, T.S., Bax, A., Cole, N.B., Nussbaum, R.L.: Structure and dynamics of micelle-bound human a-synuclein. J Biol Chem 280(10), 9595–9603 (2005). doi:10.1074/jbc.M411805200
Bodner, C.R., Dobson, C.M., Bax, A.: Multiple tight phospholipid-binding modes of a-synuclein revealed by solution NMR spectroscopy. J Mol Biol 390(4), 775–790 (2009). doi:10.1016/j.jmb.2009.05.066
Bodner, C.R., Maltsev, A.S., Dobson, C.M., Bax, A.: Differential phospholipid binding of a-synuclein variants implicated in Parkinson’s disease revealed by solution NMR spectroscopy. Biochemistry 49(5), 862–871 (2010). doi:10.1021/bi901723p
Bartels, T., Ahlstrom, L.S., Leftin, A., Kamp, F., Haass, C., Brown, M.F., Beyer, K.: The N-terminus of the intrinsically disordered protein a-synuclein triggers membrane binding and helix folding. Biophys J 99(7), 2116–2124 (2010). doi:10.1016/j.bpj.2010.06.035
Mao, Y., Shang, Z., Imai, Y., Hoshino, T., Tero, R., Tanaka, M., Yamamoto, N., Yanagisawa, K., Urisu, T.: Surface-induced phase separation of a sphingomyelin/cholesterol/ganglioside GM1-planar bilayer on mica surfaces and microdomain molecular conformation that accelerates Ab oligomerization. Biochim Biophys Acta 1798(6), 1090–1099 (2010). doi:10.1016/j.bbamem.2010.03.003
Vyas, K.A., Patel, H.V., Vyas, A.A., Schnaar, R.L.: Segregation of gangliosides GM1 and GD3 on cell membranes, isolated membrane rafts, and defined supported lipid monolayers. Biol Chem 382(2), 241–250 (2001). doi:10.1515/BC.2001.031
Lozano, M.M., Liu, Z., Sunnick, E., Janshoff, A., Kumar, K., Boxer, S.G.: Colocalization of the ganglioside G(M1) and cholesterol detected by secondary ion mass spectrometry. J Am Chem Soc 135(15), 5620–5630 (2013). doi:10.1021/ja310831m
Michel, V., Bakovic, M.: Lipid rafts in health and disease. Biol Cell Auspices Eur Cell Biol Organ 99(3), 129–140 (2007). doi:10.1042/BC20060051
Kakio, A., Nishimoto, S., Yanagisawa, K., Kozutsumi, Y., Matsuzaki, K.: Interactions of amyloid b-protein with various gangliosides in raft-like membranes: importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid. Biochemistry 41(23), 7385–7390 (2002)
Hoshino, T., Mahmood, M.I., Mori, K., Matsuzaki, K.: Binding and aggregation mechanism of amyloid b-peptides onto the GM1 ganglioside-containing lipid membrane. J Phys Chem B 117(27), 8085–8094 (2013). doi:10.1021/jp4029062
Fantini, J., Yahi, N., Garmy, N.: Cholesterol accelerates the binding of Alzheimer’s b-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation. Front Physiol 4, 120 (2013). doi:10.3389/fphys.2013.00120
Fantini, J., Yahi, N.: Molecular basis for the glycosphingolipid-binding specificity of a-synuclein: key role of tyrosine 39 in membrane insertion. J Mol Biol 408(4), 654–669 (2011). doi:10.1016/j.jmb.2011.03.009
Botto, L., Cunati, D., Coco, S., Sesana, S., Bulbarelli, A., Biasini, E., Colombo, L., Negro, A., Chiesa, R., Masserini, M., Palestini, P.: Role of lipid rafts and GM1 in the segregation and processing of prion protein. PLoS One 9(5), e98344 (2014). doi:10.1371/journal.pone.0098344
Mori, K., Mahmood, M.I., Neya, S., Matsuzaki, K., Hoshino, T.: Formation of GM1 ganglioside clusters on the lipid membrane containing sphingomyeline and cholesterol. J Phys Chem B 116(17), 5111–5121 (2012). doi:10.1021/jp207881k
Sonnino, S., Chigorno, V.: Ganglioside molecular species containing C18- and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures. Biochim Biophys Acta 1469(2), 63–77 (2000)
Sonnino, S., Prinetti, A., Nakayama, H., Yangida, M., Ogawa, H., Iwabuchi, K.: Role of very long fatty acid-containing glycosphingolipids in membrane organization and cell signaling: the model of lactosylceramide in neutrophils. Glycoconj J 26(6), 615–621 (2009). doi:10.1007/s10719-008-9215-8
Sugiura, Y., Shimma, S., Konishi, Y., Yamada, M.K., Setou, M.: Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus. PLoS One 3(9), e3232 (2008). doi:10.1371/journal.pone.0003232
Yasuda, T., Kinoshita, M., Murata, M., Matsumori, N.: Detailed comparison of deuterium quadrupole profiles between sphingomyelin and phosphatidylcholine bilayers. Biophys J 106(3), 631–638 (2014). doi:10.1016/j.bpj.2013.12.034
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-015-9587-5