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| | ==Crystal structure of mouse RANKL-RANK complex== | | ==Crystal structure of mouse RANKL-RANK complex== |
| - | <StructureSection load='3me2' size='340' side='right' caption='[[3me2]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3me2' size='340' side='right'caption='[[3me2]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3me2]] is a 2 chain structure with sequence from [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=3ME2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ME2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3me2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ME2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ME2 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></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3me4|3me4]]</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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Opgl, Rankl, Tnfsf11, Trance ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rank, Tnfrsf11a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3me2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3me2 OCA], [https://pdbe.org/3me2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3me2 RCSB], [https://www.ebi.ac.uk/pdbsum/3me2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3me2 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=3me2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3me2 OCA], [http://pdbe.org/3me2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3me2 RCSB], [http://www.ebi.ac.uk/pdbsum/3me2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3me2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes. | + | [https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] 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. [[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_MOUSE TNF11_MOUSE] 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Gao, B]] | + | [[Category: Mus musculus]] |
| - | [[Category: Liu, C Z]] | + | [[Category: Gao B]] |
| - | [[Category: Owens, R J]] | + | [[Category: Liu CZ]] |
| - | [[Category: Ren, J]] | + | [[Category: Owens RJ]] |
| - | [[Category: Stuart, D I]] | + | [[Category: Ren J]] |
| - | [[Category: Walter, S W]] | + | [[Category: Stuart DI]] |
| - | [[Category: Wu, Y]] | + | [[Category: Walter SW]] |
| - | [[Category: Zhu, X K]] | + | [[Category: Wu Y]] |
| - | [[Category: Cytokine-cytokine receptor complex]]
| + | [[Category: Zhu XK]] |
| - | [[Category: Rank]]
| + | |
| - | [[Category: Rankl]]
| + | |
| - | [[Category: Rankl-rank complex]]
| + | |
| - | [[Category: Tnf superfamily]]
| + | |
| - | [[Category: Tnfrsf11a]]
| + | |
| - | [[Category: Tnfsf11]]
| + | |
| Structural highlights
Disease
TNF11_MOUSE Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.
Function
TNF11_MOUSE 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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Bone remodeling involves bone resorption by osteoclasts and synthesis by osteoblasts and is tightly regulated by the receptor activator of the NF-kappaB ligand (RANKL)/receptor activator of the NF-kappaB (RANK)/osteoprotegerin molecular triad. RANKL, a member of the TNF superfamily, induces osteoclast differentiation, activation and survival upon interaction with its receptor RANK. The decoy receptor osteoprotegerin inhibits osteoclast formation by binding to RANKL. Imbalance in this molecular triad can result in diseases, including osteoporosis and rheumatoid arthritis. In this study, we report the crystal structures of unliganded RANK and its complex with RANKL and elucidation of critical residues for the function of the receptor pair. RANK represents the longest TNFR with four full cysteine-rich domains (CRDs) in which the CRD4 is stabilized by a sodium ion and a rigid linkage with CRD3. On association, RANK moves via a hinge region between the CRD2 and CRD3 to make close contact with RANKL; a significant structural change previously unseen in the engagement of TNFR superfamily 1A with its ligand. The high-affinity interaction between RANK and RANKL, maintained by continuous contact between the pair rather than the patched interaction commonly observed, is necessary for the function because a slightly reduced affinity induced by mutation produces significant disruption of osteoclast formation. The structures of RANK and RANKL-RANK complex and the biological data presented in the paper are essential for not only our understanding of the specific nature of the signaling mechanism and of disease-related mutations found in patients but also structure based drug design.
Structural and functional insights of RANKL-RANK interaction and signaling.,Liu C, Walter TS, Huang P, Zhang S, Zhu X, Wu Y, Wedderburn LR, Tang P, Owens RJ, Stuart DI, Ren J, Gao B J Immunol. 2010 Jun 15;184(12):6910-9. Epub 2010 May 14. PMID:20483727[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu C, Walter TS, Huang P, Zhang S, Zhu X, Wu Y, Wedderburn LR, Tang P, Owens RJ, Stuart DI, Ren J, Gao B. Structural and functional insights of RANKL-RANK interaction and signaling. J Immunol. 2010 Jun 15;184(12):6910-9. Epub 2010 May 14. PMID:20483727 doi:10.4049/jimmunol.0904033
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