Cargando…

Which Moiety Drives Gangliosides to Form Nanodomains?

[Image: see text] Gangliosides are important glycosphingolipids involved in a multitude of physiological functions. From a physicochemical standpoint, this is related to their ability to self-organize into nanoscopic domains, even at molar concentrations of one per 1000 lipid molecules. Despite rece...

Descripción completa

Detalles Bibliográficos
Autores principales: Davidović, David, Kukulka, Mercedes, Sarmento, Maria J., Mikhalyov, Ilya, Gretskaya, Natalia, Chmelová, Barbora, Ricardo, Joana C., Hof, Martin, Cwiklik, Lukasz, Šachl, Radek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316399/
https://www.ncbi.nlm.nih.gov/pubmed/37327454
http://dx.doi.org/10.1021/acs.jpclett.3c00761
_version_ 1785067702227828736
author Davidović, David
Kukulka, Mercedes
Sarmento, Maria J.
Mikhalyov, Ilya
Gretskaya, Natalia
Chmelová, Barbora
Ricardo, Joana C.
Hof, Martin
Cwiklik, Lukasz
Šachl, Radek
author_facet Davidović, David
Kukulka, Mercedes
Sarmento, Maria J.
Mikhalyov, Ilya
Gretskaya, Natalia
Chmelová, Barbora
Ricardo, Joana C.
Hof, Martin
Cwiklik, Lukasz
Šachl, Radek
author_sort Davidović, David
collection PubMed
description [Image: see text] Gangliosides are important glycosphingolipids involved in a multitude of physiological functions. From a physicochemical standpoint, this is related to their ability to self-organize into nanoscopic domains, even at molar concentrations of one per 1000 lipid molecules. Despite recent experimental and theoretical efforts suggesting that a hydrogen bonding network is crucial for nanodomain stability, the specific ganglioside moiety decisive for the development of these nanodomains has not yet been identified. Here, we combine an experimental technique achieving nanometer resolution (Förster resonance energy transfer analyzed by Monte Carlo simulations) with atomistic molecular dynamic simulations to demonstrate that the sialic acid (Sia) residue(s) at the oligosaccharide headgroup dominates the hydrogen bonding network between gangliosides, driving the formation of nanodomains even in the absence of cholesterol or sphingomyelin. Consequently, the clustering pattern of asialoGM(1), a Sia-depleted glycosphingolipid bearing three glyco moieties, is more similar to that of structurally distant sphingomyelin than that of the closely related gangliosides GM(1) and GD(1a) with one and two Sia groups, respectively.
format Online
Article
Text
id pubmed-10316399
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-103163992023-07-04 Which Moiety Drives Gangliosides to Form Nanodomains? Davidović, David Kukulka, Mercedes Sarmento, Maria J. Mikhalyov, Ilya Gretskaya, Natalia Chmelová, Barbora Ricardo, Joana C. Hof, Martin Cwiklik, Lukasz Šachl, Radek J Phys Chem Lett [Image: see text] Gangliosides are important glycosphingolipids involved in a multitude of physiological functions. From a physicochemical standpoint, this is related to their ability to self-organize into nanoscopic domains, even at molar concentrations of one per 1000 lipid molecules. Despite recent experimental and theoretical efforts suggesting that a hydrogen bonding network is crucial for nanodomain stability, the specific ganglioside moiety decisive for the development of these nanodomains has not yet been identified. Here, we combine an experimental technique achieving nanometer resolution (Förster resonance energy transfer analyzed by Monte Carlo simulations) with atomistic molecular dynamic simulations to demonstrate that the sialic acid (Sia) residue(s) at the oligosaccharide headgroup dominates the hydrogen bonding network between gangliosides, driving the formation of nanodomains even in the absence of cholesterol or sphingomyelin. Consequently, the clustering pattern of asialoGM(1), a Sia-depleted glycosphingolipid bearing three glyco moieties, is more similar to that of structurally distant sphingomyelin than that of the closely related gangliosides GM(1) and GD(1a) with one and two Sia groups, respectively. American Chemical Society 2023-06-16 /pmc/articles/PMC10316399/ /pubmed/37327454 http://dx.doi.org/10.1021/acs.jpclett.3c00761 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Davidović, David
Kukulka, Mercedes
Sarmento, Maria J.
Mikhalyov, Ilya
Gretskaya, Natalia
Chmelová, Barbora
Ricardo, Joana C.
Hof, Martin
Cwiklik, Lukasz
Šachl, Radek
Which Moiety Drives Gangliosides to Form Nanodomains?
title Which Moiety Drives Gangliosides to Form Nanodomains?
title_full Which Moiety Drives Gangliosides to Form Nanodomains?
title_fullStr Which Moiety Drives Gangliosides to Form Nanodomains?
title_full_unstemmed Which Moiety Drives Gangliosides to Form Nanodomains?
title_short Which Moiety Drives Gangliosides to Form Nanodomains?
title_sort which moiety drives gangliosides to form nanodomains?
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316399/
https://www.ncbi.nlm.nih.gov/pubmed/37327454
http://dx.doi.org/10.1021/acs.jpclett.3c00761
work_keys_str_mv AT davidovicdavid whichmoietydrivesgangliosidestoformnanodomains
AT kukulkamercedes whichmoietydrivesgangliosidestoformnanodomains
AT sarmentomariaj whichmoietydrivesgangliosidestoformnanodomains
AT mikhalyovilya whichmoietydrivesgangliosidestoformnanodomains
AT gretskayanatalia whichmoietydrivesgangliosidestoformnanodomains
AT chmelovabarbora whichmoietydrivesgangliosidestoformnanodomains
AT ricardojoanac whichmoietydrivesgangliosidestoformnanodomains
AT hofmartin whichmoietydrivesgangliosidestoformnanodomains
AT cwikliklukasz whichmoietydrivesgangliosidestoformnanodomains
AT sachlradek whichmoietydrivesgangliosidestoformnanodomains