Abstract
Poxviruses encode a number of secreted virulence factors that function to mitigate or modulate the host immune response. M-T1 is a secreted 43-kDa glycoprotein produced by the myxoma virus, a poxvirus pathogen of rabbits, that binds CC-chemokines with high affinity, blocks binding to their cognate G-protein coupled receptors, and thereby inhibits chemokine-induced leukocyte chemotaxis. The present study indicates that M-T1, but not the related vaccinia virus 35-kDa CC-chemokine-binding protein, can localize to cell surfaces through an interaction with glycosaminoglycan molecules. In addition to biochemically characterizing the nature of this interaction, we demonstrate that M-T1 can also simultaneously interact with CC-chemokines while bound to heparin, suggesting that the binding sites on M-T1 for chemokines and heparin are distinct. Furthermore, using recombinant baculovirus-expressed M-T1 truncation and internal deletion mutants, we localize the heparin-binding region of M-T1 to the C terminus of the protein, a region that contains a high abundance of basic residues and includes two clusters of basic amino acid residues that resemble Cardin and Weintraub heparin-binding consensus sequences. The ability of M-T1 to simultaneously interact with chemokines and glycosaminoglycans may enable M-T1 to tether to endothelial surfaces or extracellular matrix and capture host chemokines that are expressed close to sites of virus infection.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 30504-30513 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 276 |
| Issue number | 32 |
| DOIs | |
| State | Published - Aug 10 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Glycosaminoglycan Binding Properties of the Myxoma Virus CC-chemokine Inhibitor, M-T1. / Seet, Bruce T.; Barrett, John; Robichaud, Janine; Shilton, Brian; Singh, Rajkumari; McFadden, Douglas.
In: Journal of Biological Chemistry, Vol. 276, No. 32, 10.08.2001, p. 30504-30513.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glycosaminoglycan Binding Properties of the Myxoma Virus CC-chemokine Inhibitor, M-T1
AU - Seet, Bruce T.
AU - Barrett, John
AU - Robichaud, Janine
AU - Shilton, Brian
AU - Singh, Rajkumari
AU - McFadden, Douglas
PY - 2001/8/10
Y1 - 2001/8/10
N2 - Poxviruses encode a number of secreted virulence factors that function to mitigate or modulate the host immune response. M-T1 is a secreted 43-kDa glycoprotein produced by the myxoma virus, a poxvirus pathogen of rabbits, that binds CC-chemokines with high affinity, blocks binding to their cognate G-protein coupled receptors, and thereby inhibits chemokine-induced leukocyte chemotaxis. The present study indicates that M-T1, but not the related vaccinia virus 35-kDa CC-chemokine-binding protein, can localize to cell surfaces through an interaction with glycosaminoglycan molecules. In addition to biochemically characterizing the nature of this interaction, we demonstrate that M-T1 can also simultaneously interact with CC-chemokines while bound to heparin, suggesting that the binding sites on M-T1 for chemokines and heparin are distinct. Furthermore, using recombinant baculovirus-expressed M-T1 truncation and internal deletion mutants, we localize the heparin-binding region of M-T1 to the C terminus of the protein, a region that contains a high abundance of basic residues and includes two clusters of basic amino acid residues that resemble Cardin and Weintraub heparin-binding consensus sequences. The ability of M-T1 to simultaneously interact with chemokines and glycosaminoglycans may enable M-T1 to tether to endothelial surfaces or extracellular matrix and capture host chemokines that are expressed close to sites of virus infection.
AB - Poxviruses encode a number of secreted virulence factors that function to mitigate or modulate the host immune response. M-T1 is a secreted 43-kDa glycoprotein produced by the myxoma virus, a poxvirus pathogen of rabbits, that binds CC-chemokines with high affinity, blocks binding to their cognate G-protein coupled receptors, and thereby inhibits chemokine-induced leukocyte chemotaxis. The present study indicates that M-T1, but not the related vaccinia virus 35-kDa CC-chemokine-binding protein, can localize to cell surfaces through an interaction with glycosaminoglycan molecules. In addition to biochemically characterizing the nature of this interaction, we demonstrate that M-T1 can also simultaneously interact with CC-chemokines while bound to heparin, suggesting that the binding sites on M-T1 for chemokines and heparin are distinct. Furthermore, using recombinant baculovirus-expressed M-T1 truncation and internal deletion mutants, we localize the heparin-binding region of M-T1 to the C terminus of the protein, a region that contains a high abundance of basic residues and includes two clusters of basic amino acid residues that resemble Cardin and Weintraub heparin-binding consensus sequences. The ability of M-T1 to simultaneously interact with chemokines and glycosaminoglycans may enable M-T1 to tether to endothelial surfaces or extracellular matrix and capture host chemokines that are expressed close to sites of virus infection.
UR - http://www.scopus.com/inward/record.url?scp=0035839571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035839571&partnerID=8YFLogxK
U2 - 10.1074/jbc.M011401200
DO - 10.1074/jbc.M011401200
M3 - Article
C2 - 11369757
AN - SCOPUS:0035839571
VL - 276
SP - 30504
EP - 30513
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 32
ER -