Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity

UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection of glycosylation...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2011-09, Vol.286 (37), p.32684-32696
Main Authors: Pedersen, Johannes W., Bennett, Eric P., Schjoldager, Katrine T.-B.G., Meldal, Morten, Holmér, Andreas P., Blixt, Ola, Cló, Emiliano, Levery, Steven B., Clausen, Henrik, Wandall, Hans H.
Format: Article
Language:English
Subjects:
GalNAc
Glycobiology
Glycobiology and Extracellular Matrices
Glycopeptides - chemistry
Glycopeptides - genetics
Glycopeptides - metabolism
Glycosylation
Glycosyltransferases
Humans
Lectin
Lectins
Mucins
Mucins - chemistry
Mucins - genetics
Mucins - metabolism
N-Acetylgalactosaminyltransferases - chemistry
N-Acetylgalactosaminyltransferases - genetics
N-Acetylgalactosaminyltransferases - metabolism
Polypeptide N-acetylgalactosaminyltransferase
Protein Binding
Protein Structure, Tertiary
Substrate Specificity - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection of glycosylation sites by GalNAc-Ts: confined sequence recognition by the catalytic domain alone, and concerted recognition of acceptor sites and adjacent GalNAc-glycosylated sites by the catalytic and lectin domains, respectively. Thus far, only the catalytic domain has been shown to have peptide sequence specificity, whereas the primary function of the lectin domain is to increase affinity to previously glycosylated substrates. Whether the lectin domain also has peptide sequence selectivity has remained unclear. Using a glycopeptide array with a library of synthetic and recombinant glycopeptides based on sequences of mucins MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC7 as well as a random glycopeptide bead library, we examined the binding properties of four different lectin domains. The lectin domains of GalNAc-T1, -T2, -T3, and -T4 bound different subsets of small glycopeptides. These results indicate an additional level of complexity in the initiation step of O-glycosylation by GalNAc-Ts.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.273722