4fa8

Multi-pronged modulation of cytokine signalingMulti-pronged modulation of cytokine signaling

Structural highlights 4fa8 is a 6 chain structure with sequence from Homo sapiens and Human gammaherpesvirus 4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BARF1_EBVG Plays diverse functions in immunomodulation and oncogenicity, maybe by acting as a functional receptor for human CSF1. May inhibit interferon secretion from mononuclear cells. Exhibits oncogenic activity in vitro (By similarity). Publication Abstract from PubMed The ubiquitous EBV causes infectious mononucleosis and is associated with several types of cancers. The EBV genome encodes an early gene product, BARF1, which contributes to pathogenesis, potentially through growth-altering and immune-modulating activities, but the mechanisms for such activities are poorly understood. We have determined the crystal structure of BARF1 in complex with human macrophage-colony stimulating factor (M-CSF), a hematopoietic cytokine with pleiotropic functions in development and immune response. BARF1 and M-CSF form a high-affinity, stable, ring-like complex in both solution and the crystal, with a BARF1 hexameric ring surrounded by three M-CSF dimers in triangular array. The binding of BARF1 to M-CSF dramatically reduces but does not completely abolish M-CSF binding and signaling through its cognate receptor FMS. A three-pronged down-regulation mechanism is proposed to explain the biological effect of BARF1 on M-CSF:FMS signaling. These prongs entail control of the circulating and effective local M-CSF concentration, perturbation of the receptor-binding surface of M-CSF, and imposition of an unfavorable global orientation of the M-CSF dimer. Each prong may reduce M-CSF:FMS signaling to a limited extent but in combination may alter M-CSF:FMS signaling dramatically. The downregulating mechanism of BARF1 underlines a viral modulation strategy, and provides a basis for understanding EBV pathogenesis. Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1.,Shim AH, Chang RA, Chen X, Longnecker R, He X Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12962-7. Epub 2012 Jul 23. PMID:22826234 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Colony-stimulating factor 3D structures

spinqualitylabelsall models 4fa8, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image