5D22

Structure of ovine granulocyte-macrophage colony-stimulating factor

Summary for 5D22

• Entry DOI: 10.2210/pdb5d22/pdb
• Descriptor: Granulocyte-macrophage colony-stimulating factor, ACETATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: signaling protein, recombinant proteins, cytokine immunology, cytokine
• Biological source: Ovis aries (Sheep)
• Cellular location: Secreted: P28773
• Total number of polymer chains: 2
• Total formula weight: 29032.93

Authors

Felix, J.,Savvides, S.N. (deposition date: 2015-08-05, release date: 2016-11-16, Last modification date: 2024-11-06)

Primary citation

Felix, J.,Kandiah, E.,De Munck, S.,Bloch, Y.,van Zundert, G.C.,Pauwels, K.,Dansercoer, A.,Novanska, K.,Read, R.J.,Bonvin, A.M.,Vergauwen, B.,Verstraete, K.,Gutsche, I.,Savvides, S.N.
Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF.
Nat Commun, 7:13228-13228, 2016

PubMed 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.

PubMed: 27819269
DOI: 10.1038/ncomms13228

Experimental method

X-RAY DIFFRACTION (1.994 Å)