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== | ==Crystal structure of FASL and DcR3 complex== | ||
[[http://www.uniprot.org/uniprot/ | <StructureSection load='4msv' size='340' side='right'caption='[[4msv]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4msv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MSV 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4msv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msv OCA], [https://pdbe.org/4msv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4msv RCSB], [https://www.ebi.ac.uk/pdbsum/4msv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4msv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TNF6B_HUMAN TNF6B_HUMAN] Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.<ref>PMID:21300286</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3. | |||
Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.,Liu W, Ramagopal U, Cheng H, Bonanno JB, Toro R, Bhosle R, Zhan C, Almo SC Structure. 2016 Nov 1;24(11):2016-2023. doi: 10.1016/j.str.2016.09.009. PMID:27806260<ref>PMID:27806260</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4msv" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 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: Almo SC]] | |||
[[Category: Bhosle RC]] | |||
[[Category: Bonanno JB]] | |||
[[Category: Liu W]] | |||
[[Category: Nathenson SG]] | |||
[[Category: Ramagopal UA]] | |||
[[Category: Zhan C]] | |||
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Latest revision as of 19:41, 20 September 2023
Crystal structure of FASL and DcR3 complexCrystal structure of FASL and DcR3 complex
Structural highlights
FunctionTNF6B_HUMAN Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.[1] Publication Abstract from PubMedThe apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3. Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.,Liu W, Ramagopal U, Cheng H, Bonanno JB, Toro R, Bhosle R, Zhan C, Almo SC Structure. 2016 Nov 1;24(11):2016-2023. doi: 10.1016/j.str.2016.09.009. PMID:27806260[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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