3d85

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{{STRUCTURE_3d85| PDB=3d85 | SCENE= }}
 
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===Crystal structure of IL-23 in complex with neutralizing FAB===
 
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{{ABSTRACT_PUBMED_18708069}}
 
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==Disease==
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==Crystal structure of IL-23 in complex with neutralizing FAB==
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[[http://www.uniprot.org/uniprot/IL12B_HUMAN IL12B_HUMAN]] Defects in IL12B are a cause of Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:[http://omim.org/entry/209950 209950]]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance.<ref>PMID:9854038</ref> <ref>PMID:11753820</ref> Genetic variations in IL12B are a cause of susceptibility to psoriasis type 11 (PSORS11) [MIM:[http://omim.org/entry/612599 612599]]. Psoriasis is a common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.<ref>PMID:9854038</ref> <ref>PMID:11753820</ref>
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<StructureSection load='3d85' size='340' side='right'caption='[[3d85]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3d85]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D85 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3d85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d85 OCA], [https://pdbe.org/3d85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d85 RCSB], [https://www.ebi.ac.uk/pdbsum/3d85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d85 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
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== Function ==
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[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d8/3d85_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3d85 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Interleukin (IL)-23 is a pro-inflammatory cytokine playing a key role in the pathogenesis of several autoimmune and inflammatory diseases. We have determined the crystal structures of the heterodimeric p19-p40 IL-23 and its complex with the Fab (antigen-binding fragment) of a neutralizing antibody at 2.9 and 1.9 A, respectively. The IL-23 structure closely resembles that of IL-12. They share the common p40 subunit, and IL-23 p19 overlaps well with IL-12 p35. Along the hydrophilic heterodimeric interface, fewer charged residues are involved for IL-23 compared with IL-12. The binding site of the Fab is located exclusively on the p19 subunit, and comparison with published cytokine-receptor structures suggests that it overlaps with the IL-23 receptor binding site.
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==Function==
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Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody.,Beyer BM, Ingram R, Ramanathan L, Reichert P, Le HV, Madison V, Orth P J Mol Biol. 2008 Oct 17;382(4):942-55. Epub 2008 Aug 7. PMID:18708069<ref>PMID:18708069</ref>
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[[http://www.uniprot.org/uniprot/IL12B_HUMAN IL12B_HUMAN]] Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.<ref>PMID:11114383</ref> Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.<ref>PMID:11114383</ref> [[http://www.uniprot.org/uniprot/IL23A_HUMAN IL23A_HUMAN]] Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.<ref>PMID:11114383</ref> <ref>PMID:12023369</ref> <ref>PMID:16424222</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3d85]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D85 OCA].
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</div>
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<div class="pdbe-citations 3d85" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Antibody|Antibody]]
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[Interleukin|Interleukin]]
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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*[[3D structures of human antibody|3D structures of human antibody]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:018708069</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Beyer, B M.]]
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[[Category: Large Structures]]
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[[Category: Ingram, R.]]
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[[Category: Beyer BM]]
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[[Category: Le, H.]]
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[[Category: Ingram R]]
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[[Category: Madison, V.]]
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[[Category: Le H]]
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[[Category: Ramanathan, L.]]
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[[Category: Madison V]]
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[[Category: Reichert, P.]]
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[[Category: Ramanathan L]]
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[[Category: Fab]]
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[[Category: Reichert P]]
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[[Category: Immune system-cytokine complex]]
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[[Category: Interleukin-23]]
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Current revision

Crystal structure of IL-23 in complex with neutralizing FAB

PDB ID 3d85

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