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| | ==CRYSTAL STRUCTURE OF LIGHT AND DcR3 COMPLEX== | | ==CRYSTAL STRUCTURE OF LIGHT AND DcR3 COMPLEX== |
| - | <StructureSection load='4j6g' size='340' side='right' caption='[[4j6g]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4j6g' size='340' side='right'caption='[[4j6g]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4j6g]] 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=4J6G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J6G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4j6g]] 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=4J6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J6G 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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]]</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=CL:CHLORIDE+ION'>CL</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFSF14, HVEML, LIGHT, UNQ391/PRO726 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNFRSF6B, DCR3, TR6, UNQ186/PRO212 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4j6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j6g OCA], [https://pdbe.org/4j6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j6g RCSB], [https://www.ebi.ac.uk/pdbsum/4j6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j6g ProSAT]</span></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=4j6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j6g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j6g RCSB], [http://www.ebi.ac.uk/pdbsum/4j6g PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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. [[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> | + | [https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4j6g" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==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: Bhosle, R C]] | + | [[Category: Almo SC]] |
| - | [[Category: Bonanno, J B]] | + | [[Category: Bhosle RC]] |
| - | [[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: 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
4j6g is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.4Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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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