Gangliosides, are glycosphingolipids, present in all vertebrate plasma membranes with particular abundance in nerve cell membrane. Gangliosides can act as portals for antimicrobial peptides, hormones, viruses, lectins, toxins and pathogens. They are strategically positioned on the outer membrane and hence can participate in a large number of recognition processes. Their abundance in nerve cellmembranemakes them "likely" receptor candidates for neuropeptides. In this review we outline our work in the area of GM1-peptide/protein interaction. We have explored the effect of GM1 containing micelles/bicelles on structures of peptides, proteins as well as on denatured proteins. It has been observed that the peptides that are disordered or having random coil structure in aqueous solution, attained an ordered three-dimensional structure when interact with GM1. It is also observed that denatured proteins undergo refolding in presence of ganglioside. Peptides/ proteins show stronger interaction with membrane lipid bilayer in presence of ganglioside than that without ganglioside. This review mainly focuses on capability of ganglioside GM1 in modulating interaction, structural, location and dynamics of peptides/proteins using a number of biophysical techniques- solution NMR, DOSY, CD, fluorescence etc. © Springer Science+Business Media New York 2014.

CHAITALI MUKHOPADHYAY

Chemistry

U L KHATUN

A GAYEN

University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Glycoconjugate Journal

Capability of ganglioside GM1 in modulating interactions, structure, location and dynamics of peptides/proteins: Biophysical approaches: Interaction of ganglioside GM1 with peptides/proteins

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. © 2013 Manna, Mukhopadhyay.

Fulltext

PLoS ONE

Binding, Conformational Transition and Dimerization of Amyloid-Î² Peptide on GM1-Containing Ternary Membrane: Insights from Molecular Dynamics Simulation

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 &lt; GD1b. The results collectively indicate that increase in sialic acids on gangliosides exhibit no obvious trend but produce diversity in bicellar morphology and interactions at molecular level. © 2013 Elsevier Ireland Ltd.

Chemistry and Physics of Lipids

Gangliosides containing different numbers of sialic acids affect the morphology and structural organization of isotropic phospholipid bicelles

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. © 2013 Elsevier B.V.

Biophysical Chemistry

Interaction of bee venom toxin melittin with ganglioside GM1 bicelle

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. © 2012 Elsevier B.V. All rights reserved.

Journal	Glycoconjugate Journal
Publisher	Kluwer Academic Publishers
ISSN	0282-0080
Open Access	No