Structural insight into why S-linked glycosylation cannot adequately mimic the role of natural O-glycosylation.
Carbohydrate-binding module
Glycosylation
Molecular dynamic simulation
Nuclear magnetic resonance
Structure
Journal
International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578
Informations de publication
Date de publication:
31 Dec 2023
31 Dec 2023
Historique:
received:
21
03
2023
revised:
21
08
2023
accepted:
30
08
2023
medline:
27
11
2023
pubmed:
5
9
2023
entrez:
4
9
2023
Statut:
ppublish
Résumé
There is an increasing interest in using S-glycosylation as a replacement for the more commonly occurring O-glycosylation, aiming to enhance the resistance of glycans against chemical hydrolysis and enzymatic degradation. However, previous studies have demonstrated that these two types of glycosylation exert distinct effects on protein properties and functions. In order to elucidate the structural basis behind the observed differences, we conducted a systematic and comparative analysis of 6 differently glycosylated forms of a model glycoprotein, CBM, using NMR spectroscopy and molecular dynamic simulations. Our findings revealed that the different stabilizing effects of S- and O-glycosylation could be attributed to altered hydrogen-bonding capability between the glycan and the polypeptide chain, and their diverse impacts on binding affinity could be elucidated by examining the interactions and motion dynamics of glycans in substrate-bound states. Overall, this study underscores the pivotal role of the glycosidic linkage in shaping the function of glycosylation and advises caution when switching glycosylation types in protein glycoengineering.
Identifiants
pubmed: 37666405
pii: S0141-8130(23)03546-8
doi: 10.1016/j.ijbiomac.2023.126649
pii:
doi:
Substances chimiques
Glycoproteins
0
Polysaccharides
0
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
126649Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest There are no conflicts to declare.