Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity. / 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.
In: The Journal of Biological Chemistry, Vol. 286, No. 37, 16.09.2011, p. 32684-96.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity
AU - Pedersen, Johannes W
AU - Bennett, Eric P
AU - Schjoldager, Katrine T-B G
AU - Meldal, Morten
AU - Holmér, Andreas P
AU - Blixt, Ola
AU - Cló, Emiliano
AU - Levery, Steven B
AU - Clausen, Henrik
AU - Wandall, Hans H
PY - 2011/9/16
Y1 - 2011/9/16
N2 - UDP-GalNAc:polypeptide a-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.
AB - UDP-GalNAc:polypeptide a-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.
U2 - 10.1074/jbc.M111.273722
DO - 10.1074/jbc.M111.273722
M3 - Journal article
C2 - 21768105
VL - 286
SP - 32684
EP - 32696
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 37
ER -
ID: 35077050