7kp7: Difference between revisions
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New page: '''Unreleased structure''' The entry 7kp7 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==asymmetric mTNF-alpha hTNFR1 complex== | |||
<StructureSection load='7kp7' size='340' side='right'caption='[[7kp7]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7kp7]] is a 6 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=7KP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KP7 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]] 2.65Å</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7kp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kp7 OCA], [https://pdbe.org/7kp7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kp7 RCSB], [https://www.ebi.ac.uk/pdbsum/7kp7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kp7 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7kp7" 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]] | |||
Latest revision as of 08:55, 17 October 2024
asymmetric mTNF-alpha hTNFR1 complex
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