Issue 3, 2021

Glycan–protein interactions determine kinetics of N-glycan remodeling

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.

Graphical abstract: Glycan–protein interactions determine kinetics of N-glycan remodeling

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Article information

Article type
Paper
Submitted
29 1 2021
Accepted
13 4 2021
First published
16 4 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 917-931

Glycan–protein interactions determine kinetics of N-glycan remodeling

C. Mathew, R. G. Weiß, C. Giese, C. Lin, M. Losfeld, R. Glockshuber, S. Riniker and M. Aebi, RSC Chem. Biol., 2021, 2, 917 DOI: 10.1039/D1CB00019E

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