Abstract
The Yatapoxviruses encode a distinct class of secreted TNF-binding protein (TNF-BP) that resembles an MHC class I heavy chain but distinct from any other known TNF inhibitor. Characterization of these viral TNF inhibitors from Tanapox virus, Yaba monkey tumor virus (YMTV) and a closely related version from Swinepox virus revealed dramatically differential TNF binding specificities for different mammalian species. The Tanapox virus 2L protein (TPV-2L) formed inhibitory complexes with human TNF, and interacted with monkey and canine TNF with high affinity but rabbit TNF with low affinity. On the other hand, YMTV-2L bound human and monkey TNF with high affinity but rabbit TNF with only low affinity. The TNF-BP from swinepox virus (SPV003/148) only interacted with porcine TNF with high affinity. The observed TNF binding analysis mirrored the biological activity of these TNF- binding protein to block TNF-induced cellular cytolysis. TPV-2L and YMTV-2L also inhibited the human TNF-mediated signaling in cells but TPV-2L exhibited higher affinity for human TNF (K D, 43 pM) compared with monkey (K D, 120 pM) whereas for YMTV-2L, the affinities were reversed (human TNF K D, 440 pM; monkey TNF K D, 230 pM). The interaction domain of human TNF with TNF-binding proteins is significantly different from that of TNFRs, as determined using human TNF mutants. We conclude that these poxvirus TNF-binding proteins represent a new class of TNF inhibitors and are distinct from the viral TNF receptor homologues characterized to date.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 22517-22526 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 281 |
| Issue number | 32 |
| DOIs | |
| State | Published - Aug 11 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Variation in ligand binding specificities of a novel class of poxvirus-encoded tumor necrosis factor-binding protein. / Rahman, Masmudur; Barrett, John W.; Brouckaert, Peter; McFadden, Douglas.
In: Journal of Biological Chemistry, Vol. 281, No. 32, 11.08.2006, p. 22517-22526.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Variation in ligand binding specificities of a novel class of poxvirus-encoded tumor necrosis factor-binding protein
AU - Rahman, Masmudur
AU - Barrett, John W.
AU - Brouckaert, Peter
AU - McFadden, Douglas
PY - 2006/8/11
Y1 - 2006/8/11
N2 - The Yatapoxviruses encode a distinct class of secreted TNF-binding protein (TNF-BP) that resembles an MHC class I heavy chain but distinct from any other known TNF inhibitor. Characterization of these viral TNF inhibitors from Tanapox virus, Yaba monkey tumor virus (YMTV) and a closely related version from Swinepox virus revealed dramatically differential TNF binding specificities for different mammalian species. The Tanapox virus 2L protein (TPV-2L) formed inhibitory complexes with human TNF, and interacted with monkey and canine TNF with high affinity but rabbit TNF with low affinity. On the other hand, YMTV-2L bound human and monkey TNF with high affinity but rabbit TNF with only low affinity. The TNF-BP from swinepox virus (SPV003/148) only interacted with porcine TNF with high affinity. The observed TNF binding analysis mirrored the biological activity of these TNF- binding protein to block TNF-induced cellular cytolysis. TPV-2L and YMTV-2L also inhibited the human TNF-mediated signaling in cells but TPV-2L exhibited higher affinity for human TNF (K D, 43 pM) compared with monkey (K D, 120 pM) whereas for YMTV-2L, the affinities were reversed (human TNF K D, 440 pM; monkey TNF K D, 230 pM). The interaction domain of human TNF with TNF-binding proteins is significantly different from that of TNFRs, as determined using human TNF mutants. We conclude that these poxvirus TNF-binding proteins represent a new class of TNF inhibitors and are distinct from the viral TNF receptor homologues characterized to date.
AB - The Yatapoxviruses encode a distinct class of secreted TNF-binding protein (TNF-BP) that resembles an MHC class I heavy chain but distinct from any other known TNF inhibitor. Characterization of these viral TNF inhibitors from Tanapox virus, Yaba monkey tumor virus (YMTV) and a closely related version from Swinepox virus revealed dramatically differential TNF binding specificities for different mammalian species. The Tanapox virus 2L protein (TPV-2L) formed inhibitory complexes with human TNF, and interacted with monkey and canine TNF with high affinity but rabbit TNF with low affinity. On the other hand, YMTV-2L bound human and monkey TNF with high affinity but rabbit TNF with only low affinity. The TNF-BP from swinepox virus (SPV003/148) only interacted with porcine TNF with high affinity. The observed TNF binding analysis mirrored the biological activity of these TNF- binding protein to block TNF-induced cellular cytolysis. TPV-2L and YMTV-2L also inhibited the human TNF-mediated signaling in cells but TPV-2L exhibited higher affinity for human TNF (K D, 43 pM) compared with monkey (K D, 120 pM) whereas for YMTV-2L, the affinities were reversed (human TNF K D, 440 pM; monkey TNF K D, 230 pM). The interaction domain of human TNF with TNF-binding proteins is significantly different from that of TNFRs, as determined using human TNF mutants. We conclude that these poxvirus TNF-binding proteins represent a new class of TNF inhibitors and are distinct from the viral TNF receptor homologues characterized to date.
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U2 - 10.1074/jbc.M604645200
DO - 10.1074/jbc.M604645200
M3 - Article
C2 - 16782702
AN - SCOPUS:33747371959
VL - 281
SP - 22517
EP - 22526
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 32
ER -