View source for 2tnf


==1.4 A RESOLUTION STRUCTURE OF MOUSE TUMOR NECROSIS FACTOR, TOWARDS MODULATION OF ITS SELECTIVITY AND TRIMERISATION==
<StructureSection load='2tnf' size='340' side='right'caption='[[2tnf]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2tnf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2TNF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2TNF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2tnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2tnf OCA], [http://pdbe.org/2tnf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2tnf RCSB], [http://www.ebi.ac.uk/pdbsum/2tnf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2tnf ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/TNFA_MOUSE TNFA_MOUSE]] 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.  The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells (By similarity). 
== 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/tn/2tnf_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=2tnf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 1.4 A resolution structure of recombinant mouse tumour-necrosis factor alpha (mTNF) at 100 K has been determined. The crystals are triclinic, space group P1, with unit-cell parameters a = 48.06, b = 48.18, c = 51.01 A, alpha = 114.8, beta = 103.6, gamma = 91.1 degrees. The structure was refined to a final crystallographic R value of 19.7% (Rfree = 23.3%), including 3477 protein atoms, one 2-propanol molecule, one Tris molecule and 240 water molecules. Throughout the crystal lattice, the trimers are differently packed compared with human TNF, which was crystallized in the tetragonal space group P41212 and refined to 2.6 A resolution. The structures of mTNF and human TNF are very similar, diverging mainly in regions that are either flexible and/or involved in crystal packing. Some loops in mTNF which contain residues important for receptor binding are better resolved than in human TNF, such as the surface-exposed loops 30-34 and 144-147, which are also important for receptor specificity. Compared with human TNFs, the channel formed by the three monomers in mTNF is narrower. One 2-propanol molecule trapped in the trimeric channel could be a lead compound for the design of TNF inhibitors.

The structure of mouse tumour-necrosis factor at 1.4 A resolution: towards modulation of its selectivity and trimerization.,Baeyens KJ, De Bondt HL, Raeymaekers A, Fiers W, De Ranter CJ Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):772-8. PMID:10089307<ref>PMID:10089307</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2tnf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tumor necrosis factor|Tumor necrosis factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Baeyens, K J]]
[[Category: Bondt, H L.De]]
[[Category: Fiers, W]]
[[Category: Raeymaekers, A]]
[[Category: Ranter, C J.De]]
[[Category: Cytokine]]
[[Category: Cytotoxin]]
[[Category: Glycoprotein]]
[[Category: Lymphokine]]
[[Category: Signal-anchor]]
[[Category: Transmembrane]]