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-Structure paper
タイトル | Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF. |
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ジャーナル・号・ページ | Nat Commun, Vol. 7, Page 13228, Year 2016 |
掲載日 | 2016年11月7日 |
![]() | 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 / ![]() ![]() ![]() ![]() ![]() |
PubMed 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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 1.994 - 17.0 Å |
構造データ | ![]() EMDB-4060: ![]() PDB-5d22: ![]() PDB-5d28: |
化合物 | ![]() ChemComp-ACT: ![]() ChemComp-EDO: ![]() ChemComp-HOH: ![]() ChemComp-NAG: ![]() ChemComp-SO4: |
由来 |
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![]() | CYTOKINE / Signaling Protein / recombinant proteins / cytokine immunology / VIRAL PROTEIN / Host-pathogen interactions / Immunology |