|
|
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal Structure of mouse RANK bound to RANKL== | | ==Crystal Structure of mouse RANK bound to RANKL== |
| | <StructureSection load='4giq' size='340' side='right' caption='[[4giq]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='4giq' size='340' side='right' caption='[[4giq]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4giq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GIQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GIQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4giq]] 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=4GIQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GIQ 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=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"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3me2|3me2]], [[3qbq|3qbq]], [[3me4|3me4]], [[1jtz|1jtz]], [[3k51|3k51]], [[1d4v|1d4v]], [[1d0g|1d0g]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3me2|3me2]], [[3qbq|3qbq]], [[3me4|3me4]], [[1jtz|1jtz]], [[3k51|3k51]], [[1d4v|1d4v]], [[1d0g|1d0g]]</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 Mus musculus]), Rank, Tnfrsf11a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4giq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4giq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4giq RCSB], [http://www.ebi.ac.uk/pdbsum/4giq PDBsum]</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=4giq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4giq OCA], [http://pdbe.org/4giq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4giq RCSB], [http://www.ebi.ac.uk/pdbsum/4giq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4giq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| Line 20: |
Line 21: |
| | 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 4giq" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| Line 27: |
Line 29: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mus musculus]] | + | [[Category: Lk3 transgenic mice]] |
| | [[Category: Fremont, D H]] | | [[Category: Fremont, D H]] |
| | [[Category: Nelson, C A]] | | [[Category: Nelson, C A]] |
| Structural highlights
4giq is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 3me2, 3qbq, 3me4, 1jtz, 3k51, 1d4v, 1d0g |
| Gene: | Opgl, Rankl, Tnfsf11, Trance (LK3 transgenic mice), Rank, Tnfrsf11a (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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. [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.[1] [2]
Publication Abstract from PubMed
Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with approximately 500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis approximately 150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.
RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor.,Nelson CA, Warren JT, Wang MW, Teitelbaum SL, Fremont DH Structure. 2012 Oct 2. pii: S0969-2126(12)00334-6. doi:, 10.1016/j.str.2012.08.030. PMID:23039992[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, Morinaga T, Higashio K. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun. 1998 Dec 18;253(2):395-400. PMID:9878548 doi:S0006-291X(98)99788-1
- ↑ 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
- ↑ Nelson CA, Warren JT, Wang MW, Teitelbaum SL, Fremont DH. RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor. Structure. 2012 Oct 2. pii: S0969-2126(12)00334-6. doi:, 10.1016/j.str.2012.08.030. PMID:23039992 doi:http://dx.doi.org/10.1016/j.str.2012.08.030
|
