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

Show full item record



Permalink

http://hdl.handle.net/10138/329392

Citation

Vuorio , J , Skerlova , J , Fabry , M , Veverka , V , Vattulainen , I , Rezacova , P & Martinez-Seara , H 2021 , ' N-Glycosylation can selectively block or foster different receptor-ligand binding modes ' , Scientific Reports , vol. 11 , no. 1 , 5239 . https://doi.org/10.1038/s41598-021-84569-z

Title: N-Glycosylation can selectively block or foster different receptor-ligand binding modes
Author: Vuorio, Joni; Skerlova, Jana; Fabry, Milan; Veverka, Vaclav; Vattulainen, Ilpo; Rezacova, Pavlina; Martinez-Seara, Hector
Contributor organization: Materials Physics
Department of Physics
Date: 2021-03-04
Language: eng
Number of pages: 12
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-84569-z
URI: http://hdl.handle.net/10138/329392
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.
Subject: 114 Physical sciences
116 Chemical sciences
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41598_021_84569_z.pdf 3.947Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record