3d5o

Structural recognition and functional activation of FcrR by innate pentraxins

spinqualitylabelsall models 3d5o, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3d5o is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, NAG, SO4 Gene: FCGR2A, CD32, FCG2, FCGR2A1, IGFR2 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [SAMP_HUMAN] Note=SAP is a precursor of amyloid component P which is found in basement membrane and associated with amyloid deposits. Function [SAMP_HUMAN] Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin. [FCG2A_HUMAN] Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens. 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 Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein, which are two of the acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q (refs 3 and 4). More recently, members of the pentraxin family were found to interact with cell-surface Fcgamma receptors (FcgammaR) and activate leukocyte-mediated phagocytosis. Here we describe the structural mechanism for pentraxin's binding to FcgammaR and its functional activation of FcgammaR-mediated phagocytosis and cytokine secretion. The complex structure between human SAP and FcgammaRIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1:1 stoichiometry between SAP and FcgammaRIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for FcgammaR isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for FcgammaR binding and the inhibition of immune-complex-mediated phagocytosis by soluble pentraxins. These results establish antibody-like functions for pentraxins in the FcgammaR pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases. Structural recognition and functional activation of FcgammaR by innate pentraxins.,Lu J, Marnell LL, Marjon KD, Mold C, Du Clos TW, Sun PD Nature. 2008 Dec 18;456(7224):989-92. Epub 2008 Nov 16. PMID:19011614 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serum amyloid P-component

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