Summary for 3QBQ
| Entry DOI | 10.2210/pdb3qbq/pdb |
| Descriptor | Tumor necrosis factor ligand superfamily member 11, Tumor necrosis factor receptor superfamily member 11A (3 entities in total) |
| Functional Keywords | tumor necrosis factor (tnf) ligand-receptor superfamily fold, cytokine-cytokine receptor complex, cytokine/cytokine receptor |
| Biological source | Mus musculus (mouse) More |
| Cellular location | Isoform 1: Cell membrane; Single-pass type II membrane protein. Isoform 2: Cell membrane; Single-pass type II membrane protein. Isoform 3: Cytoplasm. Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted: O35235 Membrane; Single-pass type I membrane protein (Potential): O35305 |
| Total number of polymer chains | 4 |
| Total formula weight | 73058.15 |
| Authors | Ta, H.M.,Nguyen, G.T.T.,Jin, H.M.,Choi, J.K.,Park, H.,Kim, N.S.,Hwang, H.Y.,Kim, K.K. (deposition date: 2011-01-13, release date: 2011-03-02, Last modification date: 2024-10-16) |
| Primary citation | Ta, H.M.,Nguyen, G.T.T.,Jin, H.M.,Choi, J.K.,Park, H.,Kim, N.S.,Hwang, H.Y.,Kim, K.K. Structure-based development of a receptor activator of nuclear factor-kappaB ligand (RANKL) inhibitor peptide and molecular basis for osteopetrosis Proc.Natl.Acad.Sci.USA, 107:20281-20286, 2010 Cited by PubMed Abstract: The receptor activator of nuclear factor-κB (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. PubMed: 21059944DOI: 10.1073/pnas.1011686107 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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