3me4

Crystal structure of mouse RANK

spinqualitylabelsall models 3me4, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3me4 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL, GOL, NA, SO4 Related: 3me2 Gene: tnfrsf11a (Mus musculus) Resources: FirstGlance, OCA, RCSB, PDBsum Function [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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tumor necrosis factor receptor

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