Title : Effects of N-glycosylation on the activity and localization of
GlcNAc-6-sulfotransferase 1
Abstract :
- N-Acetylglucosamine-6-sulfotransferase-1 (GlcNAc6ST-1) is a Golgi-resident glycoprotein that is responsible for sulfation of the l-selectin ligand on endothelial cells
- Here, we report the sites at which GlcNAc6ST-1 is modified with N-linked glycans and the effects that each glycan has on enzyme activity, specificity, and localization
- We determined that glycans are added at three of four potential N-linked glycosylation sites : N196, N410, and N428
- The N428 glycan is required for the production of sulfated cell surface glycans: cells expressing a mutant enzyme lacking this glycan were unable to sulfate the sialyl Lewis X tetrasaccharide or a putative extended core 1 O-linked glycan
- The N196 and N410 glycans differentially affect sulfation of two different substrates: cells that express an enzyme lacking the N410 glycan are able to sulfate the sialyl Lewis X substrate, but produce reduced levels of a sulfated peripheral lymph node addressin epitope and cells that express an enzyme lacking the N196 glycan are able to produce a sulfated peripheral lymph node addressin epitope , but are impaired in their ability to sulfate sialyl Lewis X
- The glycans' effects on enzyme activity may be mediated, in part, by changes in enzyme localization
- While most mutants that lacked glycans localized normally within the Golgi, the N428A mutant and a mutant lacking all glycans were also found to localize ectopically
- Altered trafficking of mutants may be associated with the mechanisms by which misglycosylated enzyme is degraded
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. N-glycosylation, , GlcNAc-6-sulfotransferase 1, -, -
- 1. Golgi-resident, , Golgi-resident, N-Acetylglucosamine-6-sulfotransferase-1, -
- 1. glycoprotein, , glycoprotein, N-Acetylglucosamine-6-sulfotransferase-1, -
- 3. glycosylation, , -, -, sites
- 3. three, , -, -, N196, N410, and N428
- 8. misglycosylated, , enzyme, -, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 3. l-selectin, -, N196, N410, and N428