Back to Search
Start Over
N-Glycosylation can selectively block or foster different receptor-ligand binding modes
- Source :
- Scientific Reports, Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021), Vuorio, J, Škerlová, J, Fábry, M, Veverka, V, Vattulainen, I, Řezáčová, P & Martinez-Seara, H 2021, ' N-Glycosylation can selectively block or foster different receptor–ligand binding modes ', Scientific Reports, vol. 11, 5239 . https://doi.org/10.1038/s41598-021-84569-z
- Publication Year :
- 2020
-
Abstract
- While DNA encodes protein structure, glycans provide a complementary layer of information to protein function. As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation. However, the details of this modulation remain unclear. Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles. We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site. Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes. The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
- Subjects :
- 0301 basic medicine
Computational chemistry
Glycosylation
Magnetic Resonance Spectroscopy
Protein Conformation
Science
116 Chemical sciences
Carbohydrates
Glycobiology
Receptors, Cell Surface
114 Physical sciences
Article
03 medical and health sciences
chemistry.chemical_compound
Protein structure
NMR spectroscopy
N-linked glycosylation
Cell surface receptor
Polysaccharides
Cell Adhesion
Humans
Binding site
Hyaluronic Acid
Receptor
Multidisciplinary
Binding Sites
030102 biochemistry & molecular biology
Proteins
Ligand (biochemistry)
Receptor–ligand kinetics
carbohydrates (lipids)
030104 developmental biology
Hyaluronan Receptors
chemistry
Biophysics
Medicine
lipids (amino acids, peptides, and proteins)
Molecular modelling
Protein Binding
Post-translational modifications
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....754e394defad3e2136ef55334cc815a3