TY - JOUR
T1 - Myxoma virus T2 protein, a tumor necrosis factor (TNF) receptor homolog, is secreted as a monomer and dimer that each bind rabbit TNFα, but the dimer is a more potent TNF inhibitor
AU - Schreiber, Martha
AU - Rajarathnam, Krishna
AU - McFadden, Grant
PY - 1996
Y1 - 1996
N2 - The myxoma virus T2 (M-T2) gene expresses a secreted protein that contains significant sequence similarity to the ligand binding domains of the cellular tumor necrosis factor (TNF) receptors, specifically inhibits the cytolytic activity of rabbit TNFα and is an important virulence factor for myxoma virus infection in rabbits. M-T2 protein was overexpressed from vaccinia virus vectors, purified to apparent homogeneity, and found to specifically protect mouse and rabbit cells from lysis by rabbit TNFα at molar ratios comparable with the soluble versions of the host tumor necrosis factor receptors. M-T2 secreted from virus-infected cells is detected as both a monomer and a disulfide-linked dimer, both of which were shown by Scatchard analysis to bind rabbit TNFα (K(d) values of 170 pM and 195 pM, respectively), values that are comparable with the affinities of mammalian TNFs with their receptors. In contrast to the rabbit ligand, M-T2 interacts with mouse TNFα with a much lower affinity, K(d) of 1.7 nM, and was unable to inhibit the cytolytic activity of this ligand on mouse cells. Although both monomeric and dimeric forms bound rabbit TNFα with comparable affinity, the dimeric M-T2 protein was a far more potent inhibitor of rabbit TNFα, presumably because it can more effectively prevent dimerization of TNF receptors than can the M-T2 monomer.
AB - The myxoma virus T2 (M-T2) gene expresses a secreted protein that contains significant sequence similarity to the ligand binding domains of the cellular tumor necrosis factor (TNF) receptors, specifically inhibits the cytolytic activity of rabbit TNFα and is an important virulence factor for myxoma virus infection in rabbits. M-T2 protein was overexpressed from vaccinia virus vectors, purified to apparent homogeneity, and found to specifically protect mouse and rabbit cells from lysis by rabbit TNFα at molar ratios comparable with the soluble versions of the host tumor necrosis factor receptors. M-T2 secreted from virus-infected cells is detected as both a monomer and a disulfide-linked dimer, both of which were shown by Scatchard analysis to bind rabbit TNFα (K(d) values of 170 pM and 195 pM, respectively), values that are comparable with the affinities of mammalian TNFs with their receptors. In contrast to the rabbit ligand, M-T2 interacts with mouse TNFα with a much lower affinity, K(d) of 1.7 nM, and was unable to inhibit the cytolytic activity of this ligand on mouse cells. Although both monomeric and dimeric forms bound rabbit TNFα with comparable affinity, the dimeric M-T2 protein was a far more potent inhibitor of rabbit TNFα, presumably because it can more effectively prevent dimerization of TNF receptors than can the M-T2 monomer.
UR - http://www.scopus.com/inward/record.url?scp=0029934430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029934430&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.23.13333
DO - 10.1074/jbc.271.23.13333
M3 - Article
C2 - 8662837
AN - SCOPUS:0029934430
SN - 0021-9258
VL - 271
SP - 13333
EP - 13341
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 23
ER -