2bpd

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STRUCTURE OF MURINE DECTIN-1STRUCTURE OF MURINE DECTIN-1

Structural highlights

2bpd is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.5Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLC7A_MOUSE Lectin that functions as pattern receptor specific for beta-1,3-linked and beta-1,6-linked glucans, such as cell wall constituents from pathogenic bacteria and fungi. Necessary for the TLR2-mediated inflammatory response and for TLR2-mediated activation of NF-kappa-B. Enhances cytokine production in macrophages and dendritic cells. Mediates production of reactive oxygen species in the cell. Mediates phagocytosis of C.albicans conidia. Binds T-cells in a way that does not involve their surface glycans and plays a role in T-cell activation. Stimulates T-cell proliferation.[1] [2] [3] [4] [5] [6] [7] [8]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The murine molecule dectin-1 (known as the beta-glucan receptor in humans) is an immune cell surface receptor implicated in the immunological defense against fungal pathogens. Sequence analysis has indicated that the dectin-1 extracellular domain is a C-type lectin-like domain, and functional studies have established that it binds fungal beta-glucans. We report several dectin-1 crystal structures, including a high-resolution structure and a 2.8 angstroms resolution structure in which a short soaked natural beta-glucan is trapped in the crystal lattice. In vitro characterization of dectin-1 in the presence of its natural ligand indicates higher-order complex formation between dectin-1 and beta-glucans. These combined structural and biophysical data considerably extend the current knowledge of dectin-1 structure and function, and suggest potential mechanisms of defense against fungal pathogens.

Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function.,Brown J, O'Callaghan CA, Marshall AS, Gilbert RJ, Siebold C, Gordon S, Brown GD, Jones EY Protein Sci. 2007 Jun;16(6):1042-52. Epub 2007 May 1. PMID:17473009[9]

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

References

  1. Ariizumi K, Shen GL, Shikano S, Xu S, Ritter R 3rd, Kumamoto T, Edelbaum D, Morita A, Bergstresser PR, Takashima A. Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. J Biol Chem. 2000 Jun 30;275(26):20157-67. PMID:10779524 doi:http://dx.doi.org/10.1074/jbc.M909512199
  2. Brown GD, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature. 2001 Sep 6;413(6851):36-7. PMID:11544516 doi:http://dx.doi.org/10.1038/35092620
  3. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 2003 May 5;197(9):1107-17. Epub 2003 Apr 28. PMID:12719479 doi:http://dx.doi.org/10.1084/jem.20021787
  4. Adachi Y, Ishii T, Ikeda Y, Hoshino A, Tamura H, Aketagawa J, Tanaka S, Ohno N. Characterization of beta-glucan recognition site on C-type lectin, dectin 1. Infect Immun. 2004 Jul;72(7):4159-71. PMID:15213161 doi:http://dx.doi.org/10.1128/IAI.72.7.4159-4171.2004
  5. Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 2005 Mar 23;24(6):1277-86. Epub 2005 Feb 24. PMID:15729357 doi:http://dx.doi.org/10.1038/sj.emboj.7600594
  6. Viriyakosol S, Fierer J, Brown GD, Kirkland TN. Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1. Infect Immun. 2005 Mar;73(3):1553-60. PMID:15731053 doi:http://dx.doi.org/73/3/1553
  7. Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, Reis e Sousa C. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 2005 Apr;22(4):507-17. PMID:15845454 doi:S1074-7613(05)00095-6
  8. Yadav M, Schorey JS. The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood. 2006 Nov 1;108(9):3168-75. Epub 2006 Jul 6. PMID:16825490 doi:http://dx.doi.org/blood-2006-05-024406
  9. Brown J, O'Callaghan CA, Marshall AS, Gilbert RJ, Siebold C, Gordon S, Brown GD, Jones EY. Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function. Protein Sci. 2007 Jun;16(6):1042-52. Epub 2007 May 1. PMID:17473009 doi:10.1110/ps.072791207

2bpd, resolution 1.50Å

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