Proteomics,Multiomics

Dataset Information

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Deconstruction of the GalNAc-Type O-Glycosylation Capacity of Human HEK293 Cells


ABSTRACT: Most proteins trafficking the secretory pathway of metazoan cells will acquire GalNAc-type O-glycosylation. GalNAc-type O-glycosylation is differentially regulated in cells by the expression of a repertoire of up to twenty genes encoding polypeptide GalNAc-transferase isoforms (GalNAc-Ts) that initiate O-glycosylation by catalyzing the attachment of GalNAc residues to select Ser and Thr residues. These GalNAc-Ts orchestrate the positions and patterns of O-glycans on proteins in poorly understood coordinated ways guided partly by the kinetic properties and substrate specificities of their catalytic domains and modulatory effects of their unique GalNAc-binding lectin domains. Here, we provide the hereto most comprehensive characterization of the non-redundant contributions of individual GalNAc-T isoforms to the O-glycoproteome of the human HEK293 cell line using quantitative differential O-glycoproteomics on a panel of isogenic HEK293 cell lines with knockout of GalNAc-T genes (GALNT1, T2, T3, T7, T10, or T11). We confirm that a major part of the O-glycoproteome is covered by redundancy, while distinct subsets of O-glycosites are covered by non-redundant GalNAc-T isoform-specific functions. We demonstrate that GalNAc-T7 and T10 as predicted from in vitro studies function in completion of high density O-glycosylated regions, while GalNAc-T11 selectively controls the site-specific O-glycosylation of low-density lipoprotein-related receptors in the linker regions between the ligand-binding LDLR class A repeats.

INSTRUMENT(S): Orbitrap Fusion ETD, LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Sergey Vakhrushev  

LAB HEAD: Sergey Y. Vakhrushev

PROVIDER: PXD009955 | Pride | 2019-06-24

REPOSITORIES: Pride

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