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Article dans une revue

Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF.

Abstract : 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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Contributeur : Frank Thomas <>
Soumis le : mardi 24 novembre 2020 - 10:05:16
Dernière modification le : lundi 29 mars 2021 - 14:41:00
Archivage à long terme le : : jeudi 25 février 2021 - 18:55:25


Felix et al. Nat Comm.pdf
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Jan Felix, Eaazhisai Kandiah, Steven de Munck, Yehudi Bloch, Gydo C P van Zundert, et al.. Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF.. Nature Communications, Nature Publishing Group, 2016, 7, pp.13228. ⟨10.1038/ncomms13228⟩. ⟨hal-01443297⟩



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