The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation
Identifieur interne : 002B81 ( Main/Exploration ); précédent : 002B80; suivant : 002B82The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation
Auteurs : Hans H. Wandall [Danemark] ; Fernando Irazoqui [Danemark, Argentine] ; Mads Agervig Tarp [Danemark] ; Eric P. Bennett [Danemark] ; Ulla Mandel [Danemark] ; Hideyuki Takeuchi [Japon] ; Kentaro Kato [Danemark] ; Tatsuro Irimura [Japon] ; Ganesh Suryanarayanan [États-Unis] ; Michael A. Hollingsworth [États-Unis] ; Henrik Clausen [Danemark]Source :
- Glycobiology [ 0959-6658 ] ; 2007.
Abstract
Initiation of mucin-type O-glycosylation is controlled by a large family of UDP GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Most GalNAc-transferases contain a ricin-like lectin domain in the C-terminal end, which may confer GalNAc-glycopeptide substrate specificity to the enzyme. We have previously shown that the lectin domain of GalNAc-T4 modulates its substrate specificity to enable unique GalNAc-glycopeptide specificities and that this effect is selectively inhibitable by GalNAc; however, direct evidence of carbohydrate binding of GalNAc-transferase lectins has not been previously presented. Here, we report the direct carbohydrate binding of two GalNAc-transferase lectin domains, GalNAc-T4 and GalNAc-T2, representing isoforms reported to have distinct glycopeptide activity (GalNAc-T4) and isoforms without apparent distinct GalNAc-glycopeptide specificity (GalNAc-T2). Both lectins exhibited specificity for binding of free GalNAc. Kinetic and time-course analysis of GalNAc-T2 demonstrated that the lectin domain did not affect transfer to initial glycosylation sites, but selectively modulated velocity of transfer to subsequent sites and affected the number of acceptor sites utilized. The results suggest that GalNAc-transferase lectins serve to modulate the kinetic properties of the enzymes in the late stages of the initiation process of O-glycosylation to accomplish dense or complete O-glycan occupancy.
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DOI: 10.1093/glycob/cwl082
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Most GalNAc-transferases contain a ricin-like lectin domain in the C-terminal end, which may confer GalNAc-glycopeptide substrate specificity to the enzyme. We have previously shown that the lectin domain of GalNAc-T4 modulates its substrate specificity to enable unique GalNAc-glycopeptide specificities and that this effect is selectively inhibitable by GalNAc; however, direct evidence of carbohydrate binding of GalNAc-transferase lectins has not been previously presented. Here, we report the direct carbohydrate binding of two GalNAc-transferase lectin domains, GalNAc-T4 and GalNAc-T2, representing isoforms reported to have distinct glycopeptide activity (GalNAc-T4) and isoforms without apparent distinct GalNAc-glycopeptide specificity (GalNAc-T2). Both lectins exhibited specificity for binding of free GalNAc. Kinetic and time-course analysis of GalNAc-T2 demonstrated that the lectin domain did not affect transfer to initial glycosylation sites, but selectively modulated velocity of transfer to subsequent sites and affected the number of acceptor sites utilized. The results suggest that GalNAc-transferase lectins serve to modulate the kinetic properties of the enzymes in the late stages of the initiation process of O-glycosylation to accomplish dense or complete O-glycan occupancy.</div></front></TEI><affiliations><list><country><li>Argentine</li><li>Danemark</li><li>Japon</li><li>États-Unis</li></country><region><li>Nebraska</li><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li></orgName></list><tree><country name="Danemark"><noRegion><name sortKey="Wandall, Hans H" sort="Wandall, Hans H" uniqKey="Wandall H" first="Hans H." last="Wandall">Hans H. Wandall</name></noRegion><name sortKey="Bennett, Eric P" sort="Bennett, Eric P" uniqKey="Bennett E" first="Eric P." last="Bennett">Eric P. Bennett</name><name sortKey="Clausen, Henrik" sort="Clausen, Henrik" uniqKey="Clausen H" first="Henrik" last="Clausen">Henrik Clausen</name><name sortKey="Clausen, Henrik" sort="Clausen, Henrik" uniqKey="Clausen H" first="Henrik" last="Clausen">Henrik Clausen</name><name sortKey="Clausen, Henrik" sort="Clausen, Henrik" uniqKey="Clausen H" first="Henrik" last="Clausen">Henrik Clausen</name><name sortKey="Irazoqui, Fernando" sort="Irazoqui, Fernando" uniqKey="Irazoqui F" first="Fernando" last="Irazoqui">Fernando Irazoqui</name><name sortKey="Kato, Kentaro" sort="Kato, Kentaro" uniqKey="Kato K" first="Kentaro" last="Kato">Kentaro Kato</name><name sortKey="Mandel, Ulla" sort="Mandel, Ulla" uniqKey="Mandel U" first="Ulla" last="Mandel">Ulla Mandel</name><name sortKey="Tarp, Mads Agervig" sort="Tarp, Mads Agervig" uniqKey="Tarp M" first="Mads Agervig" last="Tarp">Mads Agervig Tarp</name></country><country name="Argentine"><noRegion><name sortKey="Irazoqui, Fernando" sort="Irazoqui, Fernando" uniqKey="Irazoqui F" first="Fernando" last="Irazoqui">Fernando Irazoqui</name></noRegion></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Takeuchi, Hideyuki" sort="Takeuchi, Hideyuki" uniqKey="Takeuchi H" first="Hideyuki" last="Takeuchi">Hideyuki Takeuchi</name></region><name sortKey="Irimura, Tatsuro" sort="Irimura, Tatsuro" uniqKey="Irimura T" first="Tatsuro" last="Irimura">Tatsuro Irimura</name></country><country name="États-Unis"><region name="Nebraska"><name sortKey="Suryanarayanan, Ganesh" sort="Suryanarayanan, Ganesh" uniqKey="Suryanarayanan G" first="Ganesh" last="Suryanarayanan">Ganesh Suryanarayanan</name></region><name sortKey="Hollingsworth, Michael A" sort="Hollingsworth, Michael A" uniqKey="Hollingsworth M" first="Michael A." last="Hollingsworth">Michael A. 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