Other formats:
BibTeX
LaTeX
RIS
@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.
|