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. 1990 Aug;87(15):5945–5949. doi: 10.1073/pnas.87.15.5945

Localization of an antiviral site on the pregnancy recognition hormone, ovine trophoblast protein 1.

C H Pontzer 1, T L Ott 1, F W Bazer 1, H M Johnson 1
PMCID: PMC54446  PMID: 2165611

Abstract

Ovine trophoblast protein 1 (oTP-1) is the interferon alpha (IFN-alpha) variant with potent antiviral activity and low toxicity that is responsible for maternal recognition of pregnancy in sheep. To examine the structure/function basis for the potent antiviral activity of oTP-1, we have exploited the direct approach of synthetic peptide competition with oTP-1 for receptor, using N-terminal oTP-1-(1-37) and C-terminal oTP-1-(139-172) peptides. These peptides possess structures similar to those predicted for the intact molecule on the basis of circular dichroism. oTP-1-(1-37) at 1.5 mM specifically blocked oTP-1 antiviral activity without affecting the antiviral activity of natural ovine IFN-alpha, recombinant bovine IFN-alpha, and recombinant human IFN-alpha. At concentrations as low as 0.15 mM, oTP-1-(139-172) blocked the antiviral activity of oTP-1, as well as that of natural ovine IFN-alpha, recombinant bovine IFN-alpha, and recombinant human IFN-alpha, but not recombinant bovine interferon gamma. Further, binding of radiolabeled oTP-1 to endometrial membrane preparations could be effectively inhibited by polyclonal anti-C-terminal and anti-N-terminal antisera, with the anti-C-terminal antiserum being the more effective inhibitor. Consistent with peptide and antiserum functional data, oTP-1 and recombinant bovine IFN-alpha are predicted to possess similar C-terminal structure but different N-terminal structure by composite surface profile predictions. The findings suggest that the C-terminal regions of IFN-alpha s bind to a common site on the IFN-alpha receptor while the N-terminal region binds to a site unique for the particular IFN-alpha.

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Selected References

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