ジャーナル: Nat Commun / 年: 2016 タイトル: Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF. 著者: Jan Felix / Eaazhisai Kandiah / Steven De Munck / Yehudi Bloch / Gydo C P van Zundert / Kris Pauwels / Ann Dansercoer / Katka Novanska / Randy J Read / Alexandre M J J Bonvin / Bjorn ...著者: Jan Felix / Eaazhisai Kandiah / Steven De Munck / Yehudi Bloch / Gydo C P van Zundert / Kris Pauwels / Ann Dansercoer / Katka Novanska / Randy J Read / Alexandre M J J Bonvin / Bjorn Vergauwen / Kenneth Verstraete / Irina Gutsche / Savvas N Savvides / 要旨: Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen ...Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen parapox Orf virus deploys GIF, a member of the poxvirus immune evasion superfamily, to antagonize GM-CSF (granulocyte macrophage colony-stimulating factor) and IL-2 (interleukin-2), two pleiotropic cytokines of the mammalian immune system. However, structural and mechanistic insights into the unprecedented functional duality of GIF have remained elusive. Here we reveal that GIF employs a dimeric binding platform that sequesters two copies of its target cytokines with high affinity and slow dissociation kinetics to yield distinct complexes featuring mutually exclusive interaction footprints. We illustrate how GIF serves as a competitive decoy receptor by leveraging binding hotspots underlying the cognate receptor interactions of GM-CSF and IL-2, without sharing any structural similarity with the cytokine receptors. Our findings contribute to the tracing of novel molecular mimicry mechanisms employed by pathogenic viruses.
タイプ: NEGATIVE / 材質: Uranyl acetate 詳細: Negatively stained EM specimens were prepared using a carbon-sandwich technique and 2% (w/v) uranyl-acetate stain.
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電子顕微鏡法
顕微鏡
JEOL 1200EXII
撮影
フィルム・検出器のモデル: KODAK SO-163 FILM / 平均電子線量: 10.0 e/Å2
電子線
加速電圧: 100 kV / 電子線源: LAB6
電子光学系
照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.0 mm / 倍率(公称値): 40000
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画像解析
初期モデル
モデルのタイプ: INSILICO MODEL In silico モデル: Ab-inition 3D reconstruction using VIPER