Structure and mechanism of IFN-γ antagonism by an orthopoxvirus IFN-γ-binding protein
- 12 February 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (6), 1861-1866
- https://doi.org/10.1073/pnas.0705753105
Abstract
Ectromelia virus (ECTV) encodes an IFN-gamma-binding protein (IFN-gammaBP(ECTV)) that disrupts IFN-gamma signaling and its ability to induce an antiviral state within cells. IFN-gammaBP(ECTV) is an important virulence factor that is highly conserved (>90%) in all orthopoxviruses, including variola virus, the causative agent of smallpox. The 2.2-A crystal structure of the IFN-gammaBP(ECTV)/IFN-gamma complex reveals IFN-gammaBP(ECTV) consists of an IFN-gammaR1 ligand-binding domain and a 57-aa helix-turn-helix (HTH) motif that is structurally related to the transcription factor TFIIA. The HTH motif forms a tetramerization domain that results in an IFN-gammaBP(ECTV)/IFN-gamma complex containing four IFN-gammaBP(ECTV) chains and two IFN-gamma dimers. The structure, combined with biochemical and cell-based assays, demonstrates that IFN-gammaBP(ECTV) tetramers are required for efficient IFN-gamma antagonism.Keywords
This publication has 33 references indexed in Scilit:
- Poxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to InfectionJournal of Virology, 2007
- Identification of residues in the ectromelia virus gamma interferon-binding protein involved in expanded species specificityJournal of General Virology, 2007
- The Unique C Termini of Orthopoxvirus Gamma Interferon Binding Proteins Are Essential for Ligand BindingJournal of Virology, 2006
- Ectromelia virus: the causative agent of mousepoxJournal of General Virology, 2005
- Interfering with interferons in inflammatory bowel diseaseGut, 2005
- The Structure and Activity of a Monomeric Interferon-γ:α-Chain Receptor Signaling ComplexStructure, 2001
- Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complexStructure, 2000
- Crystal Structure of the Yeast TFIIA/TBP/DNA ComplexScience, 1996
- Crystal structure of a yeast TFIIA/TBP/DNA complexNature, 1996
- X-Ray Structure of the GCN4 Leucine Zipper, a Two-Stranded, Parallel Coiled CoilScience, 1991