3uf2

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Crystal structure of the human Colony-Stimulating Factor 1 (hCSF-1) cytokineCrystal structure of the human Colony-Stimulating Factor 1 (hCSF-1) cytokine

Structural highlights

3uf2 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.75Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CSF1_HUMAN Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.[1] [2] Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.[3] [4]

Function

CSF1_HUMAN Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.[5] [6] [7] [8]

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[9]

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

See Also

References

  1. ↑ Chitu V, Stanley ER. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol. 2006 Feb;18(1):39-48. Epub 2005 Dec 6. PMID:16337366 doi:10.1016/j.coi.2005.11.006
  2. ↑ Patsialou A, Wyckoff J, Wang Y, Goswami S, Stanley ER, Condeelis JS. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor. Cancer Res. 2009 Dec 15;69(24):9498-506. doi: 10.1158/0008-5472.CAN-09-1868. Epub, . PMID:19934330 doi:10.1158/0008-5472.CAN-09-1868
  3. ↑ Chitu V, Stanley ER. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol. 2006 Feb;18(1):39-48. Epub 2005 Dec 6. PMID:16337366 doi:10.1016/j.coi.2005.11.006
  4. ↑ Patsialou A, Wyckoff J, Wang Y, Goswami S, Stanley ER, Condeelis JS. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor. Cancer Res. 2009 Dec 15;69(24):9498-506. doi: 10.1158/0008-5472.CAN-09-1868. Epub, . PMID:19934330 doi:10.1158/0008-5472.CAN-09-1868
  5. ↑ Chitu V, Stanley ER. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol. 2006 Feb;18(1):39-48. Epub 2005 Dec 6. PMID:16337366 doi:10.1016/j.coi.2005.11.006
  6. ↑ Patsialou A, Wyckoff J, Wang Y, Goswami S, Stanley ER, Condeelis JS. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor. Cancer Res. 2009 Dec 15;69(24):9498-506. doi: 10.1158/0008-5472.CAN-09-1868. Epub, . PMID:19934330 doi:10.1158/0008-5472.CAN-09-1868
  7. ↑ Eda H, Zhang J, Keith RH, Michener M, Beidler DR, Monahan JB. Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood. Cytokine. 2010 Dec;52(3):215-20. doi: 10.1016/j.cyto.2010.08.005. Epub 2010 Sep, 9. PMID:20829061 doi:10.1016/j.cyto.2010.08.005
  8. ↑ Wei S, Nandi S, Chitu V, Yeung YG, Yu W, Huang M, Williams LT, Lin H, Stanley ER. Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. J Leukoc Biol. 2010 Sep;88(3):495-505. doi: 10.1189/jlb.1209822. Epub 2010 May, 26. PMID:20504948 doi:10.1189/jlb.1209822
  9. ↑ 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

3uf2, resolution 2.75Å

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