Predicted structural motif of IFN tau.
Ovine interferon tau (IFN tau) is a type I interferon that was originally identified as ovine trophoblast protein and is associated with the maternal recognition of pregnancy in sheep. Additionally, IFN tau possesses potent antiviral and antiproliferative activity without the corresponding toxicity found in known IFN alpha s. Structure-function studies with synthetic peptides have identified three discontinuous functional sites on the protein that are involved in receptor interaction and biological activity. However, the structural relationship of these regions is unknown. Therefore, a model relationship of these regions is unknown. Therefore, a model of the 3-D structure of IFN tau would be useful in interpretation of existing data and the design of future structure-function studies. Combining information from circular dichroism (CD) of both the full length recombinant IFN tau and synthetic peptides representing regions of the IFN tau molecule, with sequence homology of IFN tau to IFN beta, a protein of known 3-D structure, we have constructed a model of IFN tau using distance geometry and energy minimization methods. The most striking feature of this model is that functionally active domains of IFN tau, discontinuous in the primary structure, are localized to one side of the molecule and found to be spatially contiguous. This observation is consistent with multiple binding sites on IFN tau interacting simultaneously with the IFN tau receptor.
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294.
M A
MA
Jarpe
H M
HM
Johnson
F W
FW
Bazer
T L
TL
Ott
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Curto
N R
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Krishna
C H
CH
Pontzer
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D007370:Interferon Type I / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011257:Pregnancy Proteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012756:Sheep / Q000378:metabolism; D013045:Species Specificity
D007370:Interferon Type I; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; C020947:interferon tau