Title : Partial glycosylation of
antithrombin III asparagine-135 is caused by the
serine in the third
position of its N-glycosylation consensus
sequence and is responsible for production of the beta-
antithrombin III isoform with enhanced heparin affinity
Abstract :
- Two antithrombin III ( ATIII ) isoforms occur naturally in human plasma
- The alpha- ATIII isoform has four N-linked oligosaccharides attached to asparagines 96, 135, 155, and 192
- The beta- ATIII isoform lacks carbohydrate on asparagine-135 ( N135 ), which is near the heparin binding site , and binds heparin with higher affinity than does alpha- ATIII
- Two isoforms are also produced when the normal human ATIII cDNA sequence is expressed in baculovirus-infected insect cells, and the recombinant beta' isoform similarly binds heparin with higher affinity than the recombinant alpha' isoform
- Consensus sequences ( CSs ) of the ATIII N-glycosylation sites are N-X-S for 135 and N-X-T for 96, 155, and 192
- On the basis of database and in vitro glycosylation studies suggesting that N-X-S CSs are utilized less efficiently than N-X-T CSs , we hypothesized that the beta- ATIII isoform might result from inefficient core glycosylation of the N135 N-X-S CS due to the presence of a serine , rather than a threonine , in the third position
- ATIIIs with N-X-S, N-X-T , and N-X-A consensus sequences were expressed in baculovirus-infected insect cells
- In contrast to the N-X-S sequence , which expressed a mixture of alpha' and beta' molecules, the N-X-T variant produced alpha' exclusively, while the N-X-A variant produced beta' exclusively
- Thus, serine in the third position of the N135 CS is responsible for its "partial" glycosylation and leads to production of beta- ATIII
- (ABSTRACT TRUNCATED AT 250 WORDS