Abstract
SERP-1 is a secreted serpin (serine-proteinase inhibitor) encoded by myxoma virus, a poxvirus pathogen of rabbits. SERP-1 is required for myxoma-virus virulence, and the purified protein has been shown to possess independent anti-inflammatory activity in animal models of restenosis and antigen-induced arthritis. As an inhibitor of serine proteinases, SERP-1 acts against tissue-type plasminogen activator, urokinase-type plasminogen activator, plasmin, thrombin and Factor Xa. In the present study, examination of SERP-1 glycosylation-site muta nts showed that the N-linked glycosylation of Asn172 was essential for SERP-1 secretion, whereas mutation of Asn99 decreased secretion efficiency, indicating that N-linked glycosylation plays an essential role in the processing and trafficking of SERP-1. Furthermore, comparison of SERP-1 from wild-type myxoma virus and a virus containing a targeted disruption of the MST3N sialyltransferase locus demonstrated that SERP-1 is specifically modified by this myxoma-virus-encoded sialyltransferase, and is thus the first reported viral protein shown to by modified by a virally encoded glycosyltransferase. Sialylation of SERP-1 bq the MST3N gene product creates a uniquely charged species of secreted SERP-1 that is distinct from SERP-1 produced from other eukaryotic expression systems, though this has no apparent effect upon the kinetics of in vitro proteinase inhibition. Rather, the role of viral sialylation of SERP-1 likely relates to masking antigenicity or targeting SERP-1 to specific sites of action in vitro.
Original language | English (US) |
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Pages (from-to) | 375-382 |
Number of pages | 8 |
Journal | Biochemical Journal |
Volume | 347 |
Issue number | 2 |
DOIs | |
State | Published - Apr 15 2000 |
Externally published | Yes |
Keywords
- Glycosylation
- Poxvirus
- Proteinase
- Sialylation
- Virulence factor
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology