5D28

Complex of GM-CSF/IL-2 inhibition factor with Granulocyte-macrophage colony-stimulating factor

5D28 の概要

• エントリーDOI: 10.2210/pdb5d28/pdb
• 関連するPDBエントリー: 5D22
• 分子名称: GM-CSF/IL-2 inhibition factor, Granulocyte-macrophage colony-stimulating factor, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: signaling protein, cytokine, host-pathogen interactions, immunology, viral protein
• 由来する生物種: Orf virus (ORFV); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 87805.03

構造登録者

Felix, J.,Savvides, S.N. (登録日: 2015-08-05, 公開日: 2016-11-16, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.845 Å)