View source for 7kp8


==asymmetric mTNF-alpha hTNFR1 complex==
<StructureSection load='7kp8' size='340' side='right'caption='[[7kp8]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kp8]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KP8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A7G:1-[[2-[bis(fluoranyl)methoxy]phenyl]methyl]-2-methyl-6-(6-piperazin-1-ylpyridin-3-yl)benzimidazole'>A7G</scene></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=7kp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kp8 OCA], [https://pdbe.org/7kp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kp8 RCSB], [https://www.ebi.ac.uk/pdbsum/7kp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kp8 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tumour necrosis factor (TNF) is a trimeric protein which signals through two membrane receptors, TNFR1 and TNFR2. Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. Here we present a biochemical and structural characterisation of the small molecule-stabilised TNF-TNFR1 complex, providing insights into how a distorted TNF trimer can alter signalling function. We demonstrate that the inhibitors reduce the binding affinity of TNF to the third TNFR1 molecule. In support of this, we show by X-ray crystallography that the inhibitor-bound, distorted, TNF trimer forms a complex with a dimer of TNFR1 molecules. This observation, along with data from a solution-based network assembly assay, leads us to suggest a model for TNF signalling based on TNF-TNFR1 clusters, which are disrupted by small molecule inhibitors.

Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF.,McMillan D, Martinez-Fleites C, Porter J, Fox D 3rd, Davis R, Mori P, Ceska T, Carrington B, Lawson A, Bourne T, O'Connell J Nat Commun. 2021 Jan 25;12(1):582. doi: 10.1038/s41467-020-20828-3. PMID:33495441<ref>PMID:33495441</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kp8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tumor necrosis factor 3D structures|Tumor necrosis factor 3D structures]]
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Arakaki TL]]
[[Category: Ceska T]]
[[Category: Edwards TE]]
[[Category: Foley A]]
[[Category: Fox III D]]