正痘病毒干扰素-γ结合蛋白对干扰素-γ的拮抗作用的结构与机制
Structure and mechanism of IFN-gamma antagonism by an orthopoxvirus IFN-gamma-binding protein.
作者信息
Nuara Anthony A, Walter Leigh J, Logsdon Naomi J, Yoon Sung Il, Jones Brandi C, Schriewer Jill M, Buller R Mark, Walter Mark R
机构信息
Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
出版信息
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1861-6. doi: 10.1073/pnas.0705753105. Epub 2008 Feb 5.
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.
痘苗病毒（ECTV）编码一种γ干扰素结合蛋白（IFN-γBP(ECTV)），该蛋白可破坏γ干扰素信号传导及其在细胞内诱导抗病毒状态的能力。IFN-γBP(ECTV)是一种重要的毒力因子，在所有正痘病毒中高度保守（>90%），包括天花的病原体天花病毒。IFN-γBP(ECTV)/γ干扰素复合物的2.2埃晶体结构显示，IFN-γBP(ECTV)由一个γ干扰素受体1（IFN-γR1）配体结合结构域和一个与转录因子TFIIA结构相关的57个氨基酸的螺旋-转角-螺旋（HTH）基序组成。HTH基序形成一个四聚化结构域，导致IFN-γBP(ECTV)/γ干扰素复合物包含四条IFN-γBP(ECTV)链和两个γ干扰素二聚体。该结构与生化和基于细胞的分析相结合，表明IFN-γBP(ECTV)四聚体是有效拮抗γ干扰素所必需的。
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