| Autor: |
Radhakrishnan, Ramaswamy, Walter, Leigh J., Subramaniam, Prem S., Johnson, Howard M., Walter, Mark R. |
| Zdroj: |
JMB Online (Journal of Molecular Biology); February 12, 1999, Vol. 286 Issue: 1 p151-162, 12p |
| Abstrakt: |
Ovine interferon-τ (ovIFN-τ) is a pregnancy recognition hormone required for normal embryonic development in sheep. In addition to its novel role in reproductive physiology, ovIFN-τ displays antiviral and antiproliferative activities similar to the IFN-α subtypes. To probe the structural basis for its unique activity profile, the crystal structure of ovIFN-τ has been determined at 2.1 A˚ resolution. The fold of ovIFN-τ is similar to the previously determined crystal structures of human IFN-α2b and human and murine IFN-β, which each contain five α-helices. Comparison of ovIFN-τ with huIFN-α2b, huIFN-β, and muIFN-β reveals unexpected structural differences that occur in regions of considerable sequence identity. Specifically, main-chain differences up to 11 A˚ occur for residues in helix A, the AB loop, helix B, and the BC loop. Furthermore, these regions are known to be important for receptor binding and biological activity. Of particular interest, a buried ion pair is observed in ovIFN-τ between Glu71 and Arg145 which displaces a conserved tryptophan residue (Trp77) from the helical bundle core. This ion pair represents a major change in the core of ovIFN-τ compared to huIFN-α2b. Based on amino acid sequence comparisons, these ovIFN-τ structural features may be conserved in several human IFN-α subtypes and IFN-ω. The structure identifies potential problems in interpreting site-directed mutagenesis data on the human IFN-α family that consists of 12 proteins. |
| Databáze: |
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