3qbq
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of extracellular domains of mouse RANK-RANKL complex== | |
| - | + | <StructureSection load='3qbq' size='340' side='right' caption='[[3qbq]], [[Resolution|resolution]] 2.50Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3qbq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3nzy 3nzy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QBQ FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rankl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Rank ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=3qbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qbq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qbq RCSB], [http://www.ebi.ac.uk/pdbsum/3qbq PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == 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. | [[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. | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The receptor activator of nuclear factor-kappaB (RANK) and its ligand RANKL, which belong to the tumor necrosis factor (TNF) receptor-ligand family, mediate osteoclastogenesis. The crystal structure of the RANKL ectodomain (eRANKL) in complex with the RANK ectodomain (eRANK) combined with biochemical assays of RANK mutants indicated that three RANK loops (Loop1, Loop2, and Loop3) bind to the interface of a trimeric eRANKL. Loop3 is particularly notable in that it is structurally distinctive from other TNF-family receptors and forms extensive contacts with RANKL. The disulfide bond (C125-C127) at the tip of Loop3 is important for determining the unique topology of Loop3, and docking E126 close to RANKL, which was supported by the inability of C127A or E126A mutants of RANK to bind to RANKL. Inhibitory activity of RANK mutants, which contain loops of osteoprotegerin (OPG), a soluble decoy receptor to RANKL, confirmed that OPG shares the similar binding mode with RANK and OPG. Loop3 plays a key role in RANKL binding. Peptide inhibitors designed to mimic Loop3 blocked the RANKL-induced differentiation of osteoclast precursors, suggesting that they could be developed as therapeutic agents for the treatment of osteoporosis and bone-related diseases. Furthermore, some of the RANK mutations associated with autosomal recessive osteopetrosis (ARO) resulted in reduced RANKL-binding activity and failure to induce osteoclastogenesis. These results, together with structural interpretation of eRANK-eRANKL interaction, provided molecular understanding for pathogenesis of ARO. | ||
| - | + | Structure-based development of a receptor activator of nuclear factor-{kappa}B ligand (RANKL) inhibitor peptide and molecular basis for osteopetrosis.,Ta HM, Nguyen GT, Jin HM, Choi J, Park H, Kim N, Hwang HY, Kim KK Proc Natl Acad Sci U S A. 2010 Nov 8. PMID:21059944<ref>PMID:21059944</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | + | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
| - | [[Category: Choi, J K | + | [[Category: Choi, J K]] |
| - | [[Category: Hwang, H Y | + | [[Category: Hwang, H Y]] |
| - | [[Category: Jin, H M | + | [[Category: Jin, H M]] |
| - | [[Category: Kim, K K | + | [[Category: Kim, K K]] |
| - | [[Category: Kim, N S | + | [[Category: Kim, N S]] |
| - | [[Category: Nguyen, G T.T | + | [[Category: Nguyen, G T.T]] |
| - | [[Category: Park, H | + | [[Category: Park, H]] |
| - | [[Category: Ta, H M | + | [[Category: Ta, H M]] |
[[Category: Cytokine-cytokine receptor complex]] | [[Category: Cytokine-cytokine receptor complex]] | ||
Revision as of 10:30, 19 December 2014
Crystal structure of extracellular domains of mouse RANK-RANKL complex
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