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Glycan–protein interactions determine kinetics of N-glycan remodeling
- Source :
- RSC Chemical Biology. 2:917-931
- Publication Year :
- 2021
- Publisher :
- Royal Society of Chemistry (RSC), 2021.
-
Abstract
- A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins. To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes. As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes. In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way. We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
- Subjects :
- chemistry.chemical_classification
0303 health sciences
Glycan
Glycosylation
010304 chemical physics
biology
Chemistry
Kinetics
Oligosaccharide
01 natural sciences
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Biochemistry
Protein tertiary structure
Protein–protein interaction
carbohydrates (lipids)
03 medical and health sciences
chemistry.chemical_compound
Chemistry (miscellaneous)
0103 physical sciences
biology.protein
Protein disulfide-isomerase
Glycoprotein
Molecular Biology
030304 developmental biology
Subjects
Details
- ISSN :
- 26330679
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- RSC Chemical Biology
- Accession number :
- edsair.doi...........49c01eaebf3a3bcd085880f052f7ed94