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Presence of sialic acid distinguishes gangliosides from other glycosphingolipids, helps maintain membrane structure and organization as well as acts as anchors for lectins, toxins and pathogens. The number and position of the sialic acid residues on gangliosides appear to influence the binding affinity and specificity of gangliosides. We have investigated the dependence of bicellar properties on sialic acids using monosialo1 (GM1), disialo1b (GD1b) and trisialo1a (GT1a) gangliosides incorporated in phospholipid bicelles. TEM, AFM and DLS show that increasing numbers of sialic acid moieties per ganglioside results in an increase in bicelle size. DPH fluorescence anisotropy results suggest that with incorporation of gangliosides in bicelles the orientational order of the hydrocarbon chains increases. Fluorescence anisotropy was used to explore the effect of gangliosides on lateral phase separation in ganglioside enriched bicelles. GM1 and GT1a exhibited a low Tm melting domain (DMPC rich) and a high Tm melting domain (ganglioside rich). For GD1b containing bicelles, no significant phase separation was observed, suggesting a single homogeneous phase. Symmetric and antisymmetric stretching vibrational bands of methylene shift to a lower wave number, implying acyl chain order decreasing as GT1a≪GM1

The enkephalins are endogenous neurotransmitters and bind with high affinity at the delta-receptor. Gangliosides, the major glycans of nerve cells, known to interact both with receptors and ligands on the cell surface, have been implicated to modulate the actions of opioid receptors by allosteric regulation (Wu, G.; Lu, Z. H.; Wei, T. J.; Howells, R. D.; Christoffers, K.; Leeden R. W. Ann NY Acad Sci 1998, 845, 126-138). We have studied the interactions between enkephalins and monosialylated ganglioside GM1 using NMR spectroscopy and fluorescence. The structural models of enkephalins in the presence of GM1 micelles were generated using two-dimensional (1)H-ROESY experiments along with restrained molecular dynamics simulations. We report a conformational alteration of enkephalins in the presence of GM1 micelles., (Copyright 2003 Wiley Periodicals, Inc. Biopolymers 70: 512-521, 2003)

Understanding the role of neural membrane in translocation and action of neurohormone is of great importance. Luteinizing hormone-releasing hormone (LHRH) is a neuropeptide hormone and it acts as a final signaling molecule by stimulating the synthesis of LH and FSH to maintain reproduction in all vertebrates. The receptors of LHRH are found in breast tumors and pituitary gland in the brain. Moreover, neural plasma membrane is also found to contain specific binding site for LHRH. The mechanism by which LHRH binds to membrane before it binds to the receptors is a very critical step and can have a profound impact upon the translation of peptide across the membrane. A complex form of glycosphingolipids known as Ganglioside is an important component of plasma membrane of nerve cells and breast tumor tissues. They play an important role in various physiological membrane processes. Therefore, the interaction of ganglioside-containing membrane with LHRH might be crucial in aiding the LHRH to translate through the neural membrane and reach its receptor for binding and activation. Using CD, UV-Absorbance, and fluorescence spectroscopy, the effect of Ganglioside Monosialo 1(GM1)-induced conformational changes of LHRH in the presence of Cholesterol (CHOL)/Sphingomyelin (SM) and GM1/CHOL/SM vesicles was studied. The aforesaid spectroscopic studies show that LHRH is able to bind with both the vesicles, but GM1-containing vesicles interact more effectively than vesicles without GM1. CHOL/SM vesicles partially disturb the conformation of the peptide. Moreover, binding of LHRH to GM1/CHOL/SM vesicles induces loss of conformational rigidity and attainment of a random coil. [ABSTRACT FROM AUTHOR]

Abstract: Melittin is a bee venom toxin that can act as antimicrobial peptide. Gangliosides are glycosphingolipids that help maintain membrane structure and organization as well as act as anchors for lectins, toxins, pathogens and antimicrobial peptides. Here we investigate interaction of melittin with fast tumbling isotropic control DMPC/CHAPS bicelles and ganglioside doped DMPC/CHAPS/GM1 bicelles. DOSY result shows that larger percentage of peptide binds to GM1 containing bicelles than that of the control PC bicelles. Bound peptide induces leakage of the bicelles entrapped carboxyfluorescein. Percentage of leakage is higher from control PC bicelles than that of the GM1 containing bicelles. In the presence of control PC bicelles melittin acquired fully α-helical structure. But in the presence of GM1 containing bicelles the peptide is not fully α-helical i.e., some random coil structure is present in this folded form. The present study shows that GM1 has an effect on membrane active antimicrobial peptide melittin. [Copyright &y& Elsevier]

Interactions of amyloid-β (Aβ) with neuronal membrane are associated with the progression of Alzheimer’s disease (AD). Ganglioside GM1 has been shown to promote the structural conversion of Aβ and increase the rate of peptide aggregation; but the exact nature of interaction driving theses processes remains to be explored. In this work, we have carried out atomistic-scale computer simulations (totaling 2.65 µs) to investigate the behavior of Aβ monomer and dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of GM1 was observed to act as scaffold for Aβ-binding through sugar-specific interactions. Starting from the initial helical peptide conformation, a β-hairpin motif was formed at the C-terminus of the GM1-bound Aβ-monomer; that didn’t appear in absence of GM1 (both in fluid POPC and liquid-ordered cholesterol/POPC bilayers and also in aqueous medium) within the simulation time span. For Aβ-dimers, the β-structure was further enhanced by peptide-peptide interactions, which might influence the propensity of Aβ to aggregate into higher-ordered structures. The salt-bridges and inter-peptide hydrogen bonds were found to account for dimer stability. We observed spontaneous formation of intra-peptide D23-K28 salt-bridge and a turn at V24GSN27 region - long been accepted as characteristic structural-motifs for amyloid self-assembly. Altogether, our results provide atomistic details of Aβ-GM1 and Aβ-Aβ interactions and demonstrate their importance in the early-stages of GM1-mediated Aβ-oligomerisation on membrane surface. [ABSTRACT FROM AUTHOR]

We report here the interaction of bradykinin with ganglioside GM1 by circular dichroism, steady-state fluorescence, and one-dimensional 1H NMR spectroscopy. Circular dichroism spectroscopy is indicative of a turn formation of bradykinin backbone in the presence of GM1 micelle. The fluorescence quenching efficiencies of iodide and acrylamide are substantially reduced, indicating a shielding of phenylalanine residue of bradykinin from aqueous environment. Significant line broadening of NMR resonances of bradykinin, suggestive of motional restriction, is observed. [Copyright &y& Elsevier]

We report here the interaction of melittin with ganglioside GM1 by steady-state fluorescence, one-dimensional 1H NMR spectroscopy and molecular modeling. In the presence of GM1 the emission maximum of melittin is blue shifted and fluorescence quenching efficiencies of iodide and acrylamide are substantially reduced, indicating a shielding of tryptophan of melittin from aqueous environment. Significant line broadening of NMR resonances of melittin, suggestive of motional restriction, is observed. Molecular modeling indicates a melittin–GM1 complex with N-terminal hydrophobic stretch of melittin associating with the ceramide tail and C-terminal hydrophilic end of melittin having favorable electrostatic interaction with the carbohydrate head group of GM1. [Copyright &y& Elsevier]

Abstract: Neurotensin (NT) is an endogenous tridecapeptide neurotransmitter that shows multiple biological function in central and peripheral nervous systems. Gangliosides are glycosphingolipids, most abundant in the plasma membrane of nerve cells. Here we investigate the change of neurotensin solution structure induced by isotropic CHAPS-PC bicelles with and without ganglioside GM1 using solution state NMR spectroscopy. In aqueous solution the peptide is predominately unstructured. In the presence of bicelle overall structure of the peptide is stabilized. In CHAPS-PC bicelle neurotensin adopts 310 helical structure. In the presence of GM1 containing bicelle, the peptide adopts predominately 310 helical structures with small amount of α-helical structure. These results are consistent with the CD spectroscopic results. Neurotensin interacts better with GM1 containing bicelle than that of the CHAPS-PC bicelle. Docking studies between the Neurotensin Receptor3 (NTS3) and different NT conformations also indicated better binding of the NT conformation obtained in presence of GM1-containing bicelles. [Copyright &y& Elsevier]