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Structure and mechanism of IFN-gamma antagonism by an orthopoxvirus IFN-gamma-binding protein.

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.

SUBMITTER: Nuara AA 

PROVIDER: S-EPMC2542861 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Structure and mechanism of IFN-gamma antagonism by an orthopoxvirus IFN-gamma-binding protein.

Nuara Anthony A AA   Walter Leigh J LJ   Logsdon Naomi J NJ   Yoon Sung Il SI   Jones Brandi C BC   Schriewer Jill M JM   Buller R Mark RM   Walter Mark R MR  

Proceedings of the National Academy of Sciences of the United States of America 20080205 6

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 hel  ...[more]

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