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3it8

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{{STRUCTURE_3it8| PDB=3it8 | SCENE= }}
 
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===Crystal structure of TNF alpha complexed with a poxvirus MHC-related TNF binding protein===
 
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{{ABSTRACT_PUBMED_019838188}}
 
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==Disease==
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==Crystal structure of TNF alpha complexed with a poxvirus MHC-related TNF binding protein==
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[[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[http://omim.org/entry/607507 607507]]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
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<StructureSection load='3it8' size='340' side='right'caption='[[3it8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3it8]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Yaba-like_disease_virus Yaba-like disease virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IT8 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]] 2.8&#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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=3it8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3it8 OCA], [https://pdbe.org/3it8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3it8 RCSB], [https://www.ebi.ac.uk/pdbsum/3it8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3it8 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[https://omim.org/entry/607507 607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
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== Function ==
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[https://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref>
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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/it/3it8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3it8 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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The poxvirus 2L protein binds tumor necrosis factor-alpha (TNFalpha) to inhibit host antiviral and immune responses. The 2.8-A 2L-TNFalpha structure reveals three symmetrically arranged 2L molecules per TNFalpha trimer. 2L resembles class I major histocompatibility complex (MHC) molecules but lacks a peptide-binding groove and beta2-microglobulin light chain. Overlap between the 2L and host TNF receptor-binding sites on TNFalpha rationalizes 2L inhibition of TNFalpha-TNF receptor interactions and prevention of TNFalpha-induced immune responses.
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==Function==
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Crystal structure of TNFalpha complexed with a poxvirus MHC-related TNF binding protein.,Yang Z, West AP Jr, Bjorkman PJ Nat Struct Mol Biol. 2009 Nov;16(11):1189-91. Epub 2009 Oct 18. PMID:19838188<ref>PMID:19838188</ref>
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[[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</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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[[3it8]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IT8 OCA].
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</div>
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<div class="pdbe-citations 3it8" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Tumor necrosis factor|Tumor necrosis factor]]
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== 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: Viruses]]
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[[Category: Large Structures]]
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[[Category: Bjorkman, P J.]]
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[[Category: Yaba-like disease virus]]
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[[Category: West, A P.]]
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[[Category: Bjorkman PJ]]
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[[Category: Yang, Z.]]
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[[Category: West Jr AP]]
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[[Category: Cell membrane]]
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[[Category: Yang Z]]
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[[Category: Cytokine]]
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[[Category: Disulfide bond]]
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[[Category: Glycoprotein]]
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[[Category: Immune system]]
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[[Category: Lipoprotein]]
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[[Category: Membrane]]
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[[Category: Mhc class i homolog]]
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[[Category: Myristate]]
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[[Category: Phosphoprotein]]
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[[Category: Secreted]]
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[[Category: Signal-anchor]]
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[[Category: Transmembrane]]
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Current revision

Crystal structure of TNF alpha complexed with a poxvirus MHC-related TNF binding protein

PDB ID 3it8

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