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| | <StructureSection load='6a3v' size='340' side='right'caption='[[6a3v]], [[Resolution|resolution]] 3.39Å' scene=''> | | <StructureSection load='6a3v' size='340' side='right'caption='[[6a3v]], [[Resolution|resolution]] 3.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6a3v]] is a 24 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=6A3V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A3V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6a3v]] is a 24 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=6A3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A3V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.391Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFSF9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNFRSF9, CD137, ILA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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></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=6a3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a3v OCA], [http://pdbe.org/6a3v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a3v RCSB], [http://www.ebi.ac.uk/pdbsum/6a3v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a3v ProSAT]</span></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=6a3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a3v OCA], [https://pdbe.org/6a3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a3v RCSB], [https://www.ebi.ac.uk/pdbsum/6a3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a3v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNFL9_HUMAN TNFL9_HUMAN]] Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages. [[http://www.uniprot.org/uniprot/TNR9_HUMAN TNR9_HUMAN]] Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation. | + | [https://www.uniprot.org/uniprot/TNFL9_HUMAN TNFL9_HUMAN] Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6a3v" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6a3v" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chai, Y]] | + | [[Category: Chai Y]] |
| - | [[Category: Gao, G F]] | + | [[Category: Gao GF]] |
| - | [[Category: Gao, S]] | + | [[Category: Gao S]] |
| - | [[Category: Li, Y]] | + | [[Category: Li Y]] |
| - | [[Category: Qi, J]] | + | [[Category: Qi J]] |
| - | [[Category: Tien, P]] | + | [[Category: Tien P]] |
| - | [[Category: Zhang, C]] | + | [[Category: Zhang C]] |
| - | [[Category: Agonist monoclonal antibody]]
| + | |
| - | [[Category: Complex structure]]
| + | |
| - | [[Category: Cross-linking]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
TNFL9_HUMAN Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages.
Publication Abstract from PubMed
Monoclonal antibodies (mAbs) targeting the co-stimulatory molecule 4-1BB are of interest for tumor immunotherapy. We determined the complex structures of human 4-1BB with 4-1BB ligand (4-1BBL) or utomilumab to elucidate the structural basis of 4-1BB activation. The 4-1BB/4-1BBL complex displays a typical TNF/TNFR family binding mode. The structure of utomilumab/4-1BB complex shows that utomilumab binds to dimeric 4-1BB with a distinct but partially overlapping binding area with 4-1BBL. Competitive binding analysis demonstrates that utomilumab blocks the 4-1BB/4-1BBL interaction, indicating the interruption of ligand-mediated signaling. The binding profiles of 4-1BBL and utomilumab to monomeric or dimeric 4-1BB indicate limited cross-linking of 4-1BB molecules. These findings provide mechanistic insight into the binding of 4-1BB with its ligand and its agonist mAb, which may facilitate the future development of anti-4-1BB biologics for tumor immunotherapy.
Limited Cross-Linking of 4-1BB by 4-1BB Ligand and the Agonist Monoclonal Antibody Utomilumab.,Li Y, Tan S, Zhang C, Chai Y, He M, Zhang CW, Wang Q, Tong Z, Liu K, Lei Y, Liu WJ, Liu Y, Tian Z, Cao X, Yan J, Qi J, Tien P, Gao S, Gao GF Cell Rep. 2018 Oct 23;25(4):909-920.e4. doi: 10.1016/j.celrep.2018.09.073. PMID:30355497[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li Y, Tan S, Zhang C, Chai Y, He M, Zhang CW, Wang Q, Tong Z, Liu K, Lei Y, Liu WJ, Liu Y, Tian Z, Cao X, Yan J, Qi J, Tien P, Gao S, Gao GF. Limited Cross-Linking of 4-1BB by 4-1BB Ligand and the Agonist Monoclonal Antibody Utomilumab. Cell Rep. 2018 Oct 23;25(4):909-920.e4. doi: 10.1016/j.celrep.2018.09.073. PMID:30355497 doi:http://dx.doi.org/10.1016/j.celrep.2018.09.073
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