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

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 detai...

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Autores principales:	Joni Vuorio, Jana Škerlová, Milan Fábry, Václav Veverka, Ilpo Vattulainen, Pavlína Řezáčová, Hector Martinez-Seara
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/990ff85791054a3e937ff2ae25de0092
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spelling	oai:doaj.org-article:990ff85791054a3e937ff2ae25de00922021-12-02T11:37:19ZN-Glycosylation can selectively block or foster different receptor–ligand binding modes10.1038/s41598-021-84569-z2045-2322https://doaj.org/article/990ff85791054a3e937ff2ae25de00922021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84569-zhttps://doaj.org/toc/2045-2322Abstract 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.Joni VuorioJana ŠkerlováMilan FábryVáclav VeverkaIlpo VattulainenPavlína ŘezáčováHector Martinez-SearaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joni Vuorio Jana Škerlová Milan Fábry Václav Veverka Ilpo Vattulainen Pavlína Řezáčová Hector Martinez-Seara N-Glycosylation can selectively block or foster different receptor–ligand binding modes
description	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.
format	article
author	Joni Vuorio Jana Škerlová Milan Fábry Václav Veverka Ilpo Vattulainen Pavlína Řezáčová Hector Martinez-Seara
author_facet	Joni Vuorio Jana Škerlová Milan Fábry Václav Veverka Ilpo Vattulainen Pavlína Řezáčová Hector Martinez-Seara
author_sort	Joni Vuorio
title	N-Glycosylation can selectively block or foster different receptor–ligand binding modes
title_short	N-Glycosylation can selectively block or foster different receptor–ligand binding modes
title_full	N-Glycosylation can selectively block or foster different receptor–ligand binding modes
title_fullStr	N-Glycosylation can selectively block or foster different receptor–ligand binding modes
title_full_unstemmed	N-Glycosylation can selectively block or foster different receptor–ligand binding modes
title_sort	n-glycosylation can selectively block or foster different receptor–ligand binding modes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/990ff85791054a3e937ff2ae25de0092
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N-Glycosylation can selectively block or foster different receptor–ligand binding modes

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