| Autor: |
Davidović D; J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 2155/3, 182 00 Prague, Czech Republic.; Faculty of Science, Charles University, Hlavova 8, 128 40 Prague, Czech Republic., Kukulka M; Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland., Sarmento MJ; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal., Mikhalyov I; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Gretskaya N; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Chmelová B; J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 2155/3, 182 00 Prague, Czech Republic.; Faculty of Mathematics and Physics, Charles University, Ke Karlovu, 2027/3, 121 16 Prague, Czech Republic., Ricardo JC; J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 2155/3, 182 00 Prague, Czech Republic., Hof M; J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 2155/3, 182 00 Prague, Czech Republic., Cwiklik L; J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 2155/3, 182 00 Prague, Czech Republic., Šachl R; J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 2155/3, 182 00 Prague, Czech Republic. |
| Abstrakt: |
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. |
