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@article{1815460,
author = {Sarmento, M.J. and Owen, Michael Christopher and Ricardo, J.C. and Chmelová, B. and Davidović, D. and Mikhalyov, I. and Gretskaya, N. and Hof, M. and Amaro, M. and Vácha, Robert and Šachl, R.},
article_location = {New York, USA},
article_number = {24},
doi = {http://dx.doi.org/10.1016/j.bpj.2021.11.017},
keywords = {GM1 GANGLIOSIDE; ALPHA-SYNUCLEIN; ENERGY-TRANSFER; CHOLERA-TOXIN; CELL-SURFACE; FORCE-FIELD; RECEPTOR; CHOLESTEROL; LIGANDS; DOMAINS},
language = {eng},
issn = {0006-3495},
journal = {Biophysical Journal},
title = {The impact of the glycan headgroup on the nanoscopic segregation of gangliosides.},
url = {https://www.sciencedirect.com/science/article/abs/pii/S0006349521009863?via%3Dihub},
volume = {120},
year = {2021}
}
TY - JOUR
ID - 1815460
AU - Sarmento, M.J. - Owen, Michael Christopher - Ricardo, J.C. - Chmelová, B. - Davidović, D. - Mikhalyov, I. - Gretskaya, N. - Hof, M. - Amaro, M. - Vácha, Robert - Šachl, R.
PY - 2021
TI - The impact of the glycan headgroup on the nanoscopic segregation of gangliosides.
JF - Biophysical Journal
VL - 120
IS - 24
SP - 5530-5543
EP - 5530-5543
PB - Cell Press
SN - 00063495
KW - GM1 GANGLIOSIDE
KW - ALPHA-SYNUCLEIN
KW - ENERGY-TRANSFER
KW - CHOLERA-TOXIN
KW - CELL-SURFACE
KW - FORCE-FIELD
KW - RECEPTOR
KW - CHOLESTEROL
KW - LIGANDS
KW - DOMAINS
UR - https://www.sciencedirect.com/science/article/abs/pii/S0006349521009863?via%3Dihub
N2 - Gangliosides form an important class of receptor lipids containing a large oligosaccharide headgroup whose ability to self-organize within lipid membranes results in the formation of nanoscopic platforms. Despite their biological importance, the molecular basis for the nanoscopic segregation of gangliosides is not clear. In this work, we investigated the role of the ganglioside headgroup on the nanoscale organization of gangliosides. We studied the effect of the reduction in the number of sugar units of the ganglioside oligosaccharide chain on the ability of gangliosides GM(1), GM(2), and GM(3) to spontaneously self-organize into lipid nanodomains. To reach nanoscopic resolution and to identify molecular forces that drive ganglioside segregation, we combined an experimental technique, Forster resonance energy transfer analyzed by Monte-Carlo simulations offering high lateral and trans-bilayer resolution with molecular dynamics simulations. We show that the ganglioside headgroup plays a key role in ganglioside self-assembly despite the negative charge of the sialic acid group. The nanodomains range from 7 to 120 nm in radius and are mostly composed of the surrounding bulk lipids, with gangliosides being a minor component of the nanodomains. The interactions between gangliosides are dominated by the hydrogen bonding network between the head-groups, which facilitates ganglioside clustering. The N-acetylgalactosamine sugar moiety of GM(2), however, seems to impair the stability of these clusters by disrupting hydrogen bonding of neighboring sugars, which is in agreement with a broad size distribution of GM(2) nanodomains. The simulations suggest that the formation of nanodomains is likely accompanied by several conformational changes in the gangliosides, which, however, have little impact on the solvent exposure of these receptor groups. Overall, this work identifies the key physicochemical factors that drive nanoscopic segregation of gangliosides.
ER -
SARMENTO, M.J., Michael Christopher OWEN, J.C. RICARDO, B. CHMELOVÁ, D. DAVIDOVI$\backslash$'C, I. MIKHALYOV, N. GRETSKAYA, M. HOF, M. AMARO, Robert VÁCHA and R. ŠACHL. The impact of the glycan headgroup on the nanoscopic segregation of gangliosides. \textit{Biophysical Journal}. New York, USA: Cell Press, 2021, vol.~120, No~24, p.~5530-5543. ISSN~0006-3495. Available from: https://dx.doi.org/10.1016/j.bpj.2021.11.017.
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