Published in

Nature Research, Nature Communications, 1(7), 2016

DOI: 10.1038/ncomms13228

Links

Tools

Export citation

Search in Google Scholar

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

Journal article published in 2016 by Jan Félix, Eaazhisai Kandiah ORCID, Steven De Munck, Yehudi Bloch, Gydo Cp P. van Zundert, Gydo C. P. Van Zundert, Kris Pauwels ORCID, Ann Dansercoer, Katka Novanska, Randy J. Read ORCID, Alexandre Mjj J. J. Bonvin, Bjorn Vergauwen, Kenneth Verstraete, Irina Gutsche, Savvas N. Savvides
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

SeriesInformation ; Nature Communications 7, 13228 (2016). doi:10.1038/ncomms13228 ; 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. ; Other ; Published by Nature Publishing Group, London