View source for 3it8


==Crystal structure of TNF alpha complexed with a poxvirus MHC-related TNF binding protein==
<StructureSection load='3it8' size='340' side='right'caption='[[3it8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3it8]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Tanapox_virus_strain_davis Tanapox virus strain davis]. 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>
</td></tr><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>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNF ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 2L ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=132475 Tanapox virus strain Davis])</td></tr>
<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>
</table>
== Disease ==
[[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). 
== Function ==
[[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>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/it/3it8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3it8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tumor necrosis factor|Tumor necrosis factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Tanapox virus strain davis]]
[[Category: Bjorkman, P J]]
[[Category: West, A P]]
[[Category: Yang, Z]]
[[Category: Cell membrane]]
[[Category: Cytokine]]
[[Category: Disulfide bond]]
[[Category: Glycoprotein]]
[[Category: Immune system]]
[[Category: Lipoprotein]]
[[Category: Membrane]]
[[Category: Mhc class i homolog]]
[[Category: Myristate]]
[[Category: Phosphoprotein]]
[[Category: Secreted]]
[[Category: Signal-anchor]]
[[Category: Transmembrane]]