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| | ==Human RANKL/OPG complex== | | ==Human RANKL/OPG complex== |
| - | <StructureSection load='3urf' size='340' side='right' caption='[[3urf]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='3urf' size='340' side='right'caption='[[3urf]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3urf]] is a 2 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=3URF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3URF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3urf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3URF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3URF 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='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='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]), TNFRSF11B, OCIF, OPG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFSF11, OPGL, RANKL, TRANCE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNFRSF11B, OCIF, OPG ([https://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=3urf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3urf OCA], [http://pdbe.org/3urf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3urf RCSB], [http://www.ebi.ac.uk/pdbsum/3urf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3urf 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=3urf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3urf OCA], [https://pdbe.org/3urf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3urf RCSB], [https://www.ebi.ac.uk/pdbsum/3urf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3urf 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. [[http://www.uniprot.org/uniprot/TR11B_HUMAN TR11B_HUMAN]] Juvenile Paget disease. 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. [[https://www.uniprot.org/uniprot/TR11B_HUMAN TR11B_HUMAN]] Juvenile Paget disease. 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/TR11B_HUMAN TR11B_HUMAN]] Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.<ref>PMID:22664871</ref> <ref>PMID:9168977</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> [[https://www.uniprot.org/uniprot/TR11B_HUMAN TR11B_HUMAN]] Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.<ref>PMID:22664871</ref> <ref>PMID:9168977</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/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Lu, Q Y]] | | [[Category: Lu, Q Y]] |
| | [[Category: Luan, X D]] | | [[Category: Luan, X D]] |
| Structural highlights
3urf is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Gene: | TNFSF11, OPGL, RANKL, TRANCE (HUMAN), TNFRSF11B, OCIF, OPG (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[TNF11_HUMAN] Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry. [TR11B_HUMAN] Juvenile Paget disease. 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] [TR11B_HUMAN] Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.[2] [3]
Publication Abstract from PubMed
Receptor activator of NF-kappaB ligand (RANKL), its signaling receptor RANK, and its decoy receptor osteoprotegerin (OPG) constitute a molecular triad that is critical in regulating bone remodeling, and also plays multiple roles in the immune system. OPG binds RANKL directly to block its interaction with RANK. In this article, we report the 2.7-A crystal structure of human RANKL trimer in complex with the N-terminal fragment of human OPG containing four cysteine-rich TNFR homologous domains (OPG-CRD). The structure shows that RANKL trimer uses three equivalent grooves between two neighboring monomers to interact with three OPG-CRD monomers symmetrically. A loop from the CRD3 domain of OPG-CRD inserts into the shallow groove of RANKL, providing the major binding determinant that is further confirmed by affinity measurement and osteoclast differentiation assay. These results, together with a previously reported mouse RANKL/RANK complex structure, reveal that OPG exerts its decoy receptor function by directly blocking the accessibilities of important interacting residues of RANKL for RANK recognition. Structural comparison with TRAIL/death receptor 5 complex also reveals structural basis for the cross-reactivity of OPG to TRAIL.
Crystal Structure of Human RANKL Complexed with Its Decoy Receptor Osteoprotegerin.,Luan X, Lu Q, Jiang Y, Zhang S, Wang Q, Yuan H, Zhao W, Wang J, Wang X J Immunol. 2012 Jul 1;189(1):245-52. Epub 2012 Jun 4. PMID:22664871[4]
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
- ↑ 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
- ↑ Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun. 1997 May 8;234(1):137-42. PMID:9168977
- ↑ 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
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