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

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00541209" target="_blank" >RIV/61388963:_____/21:00541209 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/21:00544836 RIV/00216208:11310/21:10439306
Result on the web
<a href="https://doi.org/10.1038/s41598-021-84569-z" target="_blank" >https://doi.org/10.1038/s41598-021-84569-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-021-84569-z" target="_blank" >10.1038/s41598-021-84569-z</a>

Result language
angličtina
Original language name
N-Glycosylation can selectively block or foster different receptor–ligand binding modes
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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