4adf

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CRYSTAL STRUCTURE OF THE HUMAN COLONY-STIMULATING FACTOR 1 (hCSF-1) CYTOKINE IN COMPLEX WITH THE VIRAL RECEPTOR BARF1CRYSTAL STRUCTURE OF THE HUMAN COLONY-STIMULATING FACTOR 1 (hCSF-1) CYTOKINE IN COMPLEX WITH THE VIRAL RECEPTOR BARF1

Structural highlights

4adf is a 24 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.
Method:X-ray diffraction, Resolution 4.4Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BARF1_EBVB9 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.[1] [2] [3]

Publication Abstract from PubMed

Hematopoietic human colony-stimulating factor 1 (hCSF-1) is essential for innate and adaptive immunity against viral and microbial infections and cancer. The human pathogen Epstein-Barr virus secretes the lytic-cycle protein BARF1 that neutralizes hCSF-1 to achieve immunomodulation. Here we show that BARF1 binds the dimer interface of hCSF-1 with picomolar affinity, away from the cognate receptor-binding site, to establish a long-lived complex featuring three hCSF-1 at the periphery of the BARF1 toroid. BARF1 locks dimeric hCSF-1 into an inactive conformation, rendering it unable to signal via its cognate receptor on human monocytes. This reveals a new functional role for hCSF-1 cooperativity in signaling. We propose a new viral strategy paradigm featuring an allosteric decoy receptor of the competitive type, which couples efficient sequestration and inactivation of the host growth factor to abrogate cooperative assembly of the cognate signaling complex.

Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1.,Elegheert J, Bracke N, Pouliot P, Gutsche I, Shkumatov AV, Tarbouriech N, Verstraete K, Bekaert A, Burmeister WP, Svergun DI, Lambrecht BN, Vergauwen B, Savvides SN Nat Struct Mol Biol. 2012 Sep;19(9):938-47. doi: 10.1038/nsmb.2367. Epub 2012 Aug, 19. PMID:22902366[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Sall A, Caserta S, Jolicoeur P, Franqueville L, de Turenne-Tessier M, Ooka T. Mitogenic activity of Epstein-Barr virus-encoded BARF1 protein. Oncogene. 2004 Jun 17;23(28):4938-44. PMID:15064715 doi:10.1038/sj.onc.1207607
  2. ↑ Seto E, Yang L, Middeldorp J, Sheen TS, Chen JY, Fukayama M, Eizuru Y, Ooka T, Takada K. Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression. J Med Virol. 2005 May;76(1):82-8. PMID:15778977 doi:10.1002/jmv.20327
  3. ↑ Wang Q, Tsao SW, Ooka T, Nicholls JM, Cheung HW, Fu S, Wong YC, Wang X. Anti-apoptotic role of BARF1 in gastric cancer cells. Cancer Lett. 2006 Jul 8;238(1):90-103. Epub 2005 Jul 27. PMID:16054293 doi:10.1016/j.canlet.2005.06.023
  4. ↑ Elegheert J, Bracke N, Pouliot P, Gutsche I, Shkumatov AV, Tarbouriech N, Verstraete K, Bekaert A, Burmeister WP, Svergun DI, Lambrecht BN, Vergauwen B, Savvides SN. Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1. Nat Struct Mol Biol. 2012 Sep;19(9):938-47. doi: 10.1038/nsmb.2367. Epub 2012 Aug, 19. PMID:22902366 doi:10.1038/nsmb.2367

4adf, resolution 4.40Å

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