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| | <StructureSection load='5bnq' size='340' side='right'caption='[[5bnq]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='5bnq' size='340' side='right'caption='[[5bnq]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bnq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BNQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BNQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bnq]] is a 2 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=5BNQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BNQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFSF11, OPGL, RANKL, TRANCE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Tnfrsf11a, Rank ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5bnq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnq OCA], [http://pdbe.org/5bnq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bnq RCSB], [http://www.ebi.ac.uk/pdbsum/5bnq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bnq 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=5bnq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnq OCA], [https://pdbe.org/5bnq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bnq RCSB], [https://www.ebi.ac.uk/pdbsum/5bnq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bnq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TNF11_HUMAN TNF11_HUMAN]] Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/TNF11_HUMAN TNF11_HUMAN] Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNF11_HUMAN TNF11_HUMAN]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.<ref>PMID:22664871</ref> [[http://www.uniprot.org/uniprot/TNR11_MOUSE TNR11_MOUSE]] Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells.<ref>PMID:9878548</ref> <ref>PMID:20483727</ref> | + | [https://www.uniprot.org/uniprot/TNF11_HUMAN TNF11_HUMAN] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.<ref>PMID:22664871</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 ligand superfamily|Tumor necrosis factor ligand superfamily]] | + | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] |
| - | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | + | *[[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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ren, J]] | + | [[Category: Ren J]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Rank]]
| + | |
| - | [[Category: Rankl]]
| + | |
| - | [[Category: Rankl-rank complex]]
| + | |
| - | [[Category: Tnf superfamily]]
| + | |
| - | [[Category: Tnfrsf11a]]
| + | |
| - | [[Category: Tnfsf11]]
| + | |
| Structural highlights
Disease
TNF11_HUMAN Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry.
Function
TNF11_HUMAN Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.[1]
Publication Abstract from PubMed
Anti-cytokine therapeutic antibodies have been demonstrated to be effective in the treatment of several auto-immune disorders. However, The problems in antibody manufacture and the immunogenicity caused by multiple doses of antibodies inspire people to use auto-cytokine as immunogen to induce anti-cytokine antibodies. Nevertheless, the tolerance for inducing immune response against self-antigen has hindered the wide application of the strategy. To overcome the tolerance, here we proposed a strategy using the inter-species cytokine as immunogen for active immunization (TISCAI) to induce anti-cytokine antibody. As a proof of concept, an inter-species cytokine RANKL was successfully used as immunogen to induce anti-RANKL immune response. Furthermore, to prevent undesirable side-effects, the human RANKL was mutated based on the crystal structure of the complex of human RANKL and its rodent counterpart receptor RANK. We found, the antibodies produced blocked the osteoclast development in vitro and osteoporosis in OVX rat models. The results demonstrated this strategy adopted is very useful for general anti-cytokine immunotherapy for different diseases settings.
A RANKL mutant used as an inter-species vaccine for efficient immunotherapy of osteoporosis.,Liu C, Zhao Y, He W, Wang W, Chen Y, Zhang S, Ma Y, Gohda J, Ishida T, Walter TS, Owens RJ, Stuart DI, Ren J, Gao B Sci Rep. 2015 Sep 28;5:14150. doi: 10.1038/srep14150. PMID:26412210[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Luan X, Lu Q, Jiang Y, Zhang S, Wang Q, Yuan H, Zhao W, Wang J, Wang X. Crystal Structure of Human RANKL Complexed with Its Decoy Receptor Osteoprotegerin. J Immunol. 2012 Jul 1;189(1):245-52. Epub 2012 Jun 4. PMID:22664871 doi:10.4049/jimmunol.1103387
- ↑ Liu C, Zhao Y, He W, Wang W, Chen Y, Zhang S, Ma Y, Gohda J, Ishida T, Walter TS, Owens RJ, Stuart DI, Ren J, Gao B. A RANKL mutant used as an inter-species vaccine for efficient immunotherapy of osteoporosis. Sci Rep. 2015 Sep 28;5:14150. doi: 10.1038/srep14150. PMID:26412210 doi:http://dx.doi.org/10.1038/srep14150
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