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| | ==Crystal structure of a human light loop mutant in complex with dcr3== | | ==Crystal structure of a human light loop mutant in complex with dcr3== |
| - | <StructureSection load='4kgq' size='340' side='right' caption='[[4kgq]], [[Resolution|resolution]] 2.27Å' scene=''> | + | <StructureSection load='4kgq' size='340' side='right'caption='[[4kgq]], [[Resolution|resolution]] 2.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kgq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KGQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kgq]] is a 4 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=4KGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KGQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4en0|4en0]], [[3k51|3k51]], [[3mi8|3mi8]], [[3mhd|3mhd]], [[4j6g|4j6g]]</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=4kgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kgq OCA], [https://pdbe.org/4kgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kgq RCSB], [https://www.ebi.ac.uk/pdbsum/4kgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kgq ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF6B, DCR3, TR6, UNQ186/PRO212 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNFSF14, HVEML, LIGHT, UNQ391/PRO726 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kgq OCA], [http://pdbe.org/4kgq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kgq RCSB], [http://www.ebi.ac.uk/pdbsum/4kgq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kgq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/TNF14_HUMAN TNF14_HUMAN]] Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | + | *[[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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Almo, S C]] | + | [[Category: Large Structures]] |
| - | [[Category: Bonanno, J B]] | + | [[Category: Almo SC]] |
| - | [[Category: IFN, Atoms-to-Animals:.The Immune Function Network]] | + | [[Category: Bonanno JB]] |
| - | [[Category: Liu, W]] | + | [[Category: Liu W]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Nathenson SG]] |
| - | [[Category: Nathenson, S G]] | + | [[Category: Sampathkumar P]] |
| - | [[Category: Sampathkumar, P]] | + | [[Category: Toro R]] |
| - | [[Category: Toro, R]] | + | [[Category: Zhan C]] |
| - | [[Category: Zhan, C]] | + | |
| - | [[Category: Atoms-to-animals: the immune function network]]
| + | |
| - | [[Category: Bind tnf receptor hvem and ltbr]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Dcr3]]
| + | |
| - | [[Category: Ifn]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Jelly-roll fold]]
| + | |
| - | [[Category: Light]]
| + | |
| - | [[Category: Ltbr]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: N-glycosylation]]
| + | |
| - | [[Category: New hvem]]
| + | |
| - | [[Category: Nysgrc]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Secreted protein]]
| + | |
| - | [[Category: Tnf]]
| + | |
| - | [[Category: Tnf14]]
| + | |
| - | [[Category: Tnfr]]
| + | |
| Structural highlights
Function
TNF6B_HUMAN Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.[1]
Publication Abstract from PubMed
LIGHT initiates intracellular signaling via engagement of the two TNF receptors, HVEM and LTbetaR. In humans, LIGHT is neutralized by DcR3, a unique soluble member of the TNFR superfamily, which tightly binds LIGHT and inhibits its interactions with HVEM and LTbetaR. DcR3 also neutralizes two other TNF ligands, FasL and TL1A. Due to its ability to neutralize three distinct different ligands, DcR3 contributes to a wide range of biological and pathological processes, including cancer and autoimmune diseases. However, the mechanisms that support the broad specificity of DcR3 remain to be fully defined. We report the structures of LIGHT and the LIGHT:DcR3 complex, which reveal the structural basis for the DcR3-mediated neutralization of LIGHT and afford insights into DcR3 function and binding promiscuity. Based on these structures, we designed LIGHT mutants with altered affinities for DcR3 and HVEM, which may represent mechanistically informative probe reagents.
Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly.,Liu W, Zhan C, Cheng H, Kumar PR, Bonanno JB, Nathenson SG, Almo SC Structure. 2014 Sep 2;22(9):1252-62. doi: 10.1016/j.str.2014.06.013. Epub 2014, Jul 31. PMID:25087510[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhan C, Patskovsky Y, Yan Q, Li Z, Ramagopal U, Cheng H, Brenowitz M, Hui X, Nathenson SG, Almo SC. Decoy Strategies: The Structure of TL1A:DcR3 Complex. Structure. 2011 Feb 9;19(2):162-71. PMID:21300286 doi:10.1016/j.str.2010.12.004
- ↑ Liu W, Zhan C, Cheng H, Kumar PR, Bonanno JB, Nathenson SG, Almo SC. Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly. Structure. 2014 Sep 2;22(9):1252-62. doi: 10.1016/j.str.2014.06.013. Epub 2014, Jul 31. PMID:25087510 doi:http://dx.doi.org/10.1016/j.str.2014.06.013
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