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Figure 4
Stereo view of IFN-τ model. Highlighted sequences are from 1–37, 62–92,
and 139–172.
Page 445
fide bridges between residues 1 and 99 and residues 29 and 139. Several structures were generated using
distance geometry routines, and the energy was minimized and averaged to yield a final model [16]. A
similar model was built by Senda et al. (unpublished results) using a homology modeling method. This
model was also built using the x-ray coordinates of IFN-β and shows a similar topology to the IFN-β
three-dimensional structure (Figure 4). The most striking feature of both models is that those
discontinuous regions, previously determined to be functionally important, are localized to one side of
the molecule and found to be spatially contiguous (Figure 4). This observation is consistent with
multiple binding sites on IFN-τ interacting simultaneously with the Type I IFN receptor and emphasizes
the importance of structural modeling in the understanding and interpretation of functional data.
III. Type II IFN
A. Functional Sites on the IFN-γ Molecule
The production of IFN-γ-neutralizing antibodies specific for an N-terminal peptide of human IFN-γ
provided the first evidence that the N-terminus of IFN-γ contained an important functional site [27]. A
similar approach was used to produce N-terminus-specific neutralizing antisera against murine IFN-γ
[28]. Subsequent studies using IFN-γ synthetic peptides to map the epitope specificity of monoclonal
antibodies to murine IFN-γ showed that N-terminal specific monoclonal antibodies neutralize IFN-γ
antiviral activity [29]. In receptor-
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