N-Glycosylation can selectively block or foster different receptor–ligand binding modes

0541209 - ÚOCHB 2022 RIV GB eng J - Článek v odborném periodiku
Vuorio, J. - Škerlová, Jana - Fábry, M. - Veverka, Václav - Vattulainen, I. - Řezáčová, Pavlína - Martinez-Seara, Hector
N-Glycosylation can selectively block or foster different receptor–ligand binding modes.
Scientific Reports. Roč. 11, č. 1 (2021), č. článku 5239. ISSN 2045-2322. E-ISSN 2045-2322
Grant CEP: GA MŠMT(CZ) EF16_019/0000729; GA ČR(CZ) GA19-19561S; GA MŠMT(CZ) LO1304
Institucionální podpora: RVO:61388963
Klíčová slova: glycosylation * ligand binding * sugar-protein interaction
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.997, rok: 2021
Způsob publikování: Open access
https://doi.org/10.1038/s41598-021-84569-z

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.
Trvalý link: http://hdl.handle.net/11104/0318805