1JTZ
CRYSTAL STRUCTURE OF TRANCE/RANKL CYTOKINE.
Summary for 1JTZ
| Entry DOI | 10.2210/pdb1jtz/pdb |
| Descriptor | TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 11 (2 entities in total) |
| Functional Keywords | tumor necrosis factor superfamily member, jellyroll, beta-sandwich, cytokine |
| Biological source | Mus musculus (house mouse) |
| 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 |
| Total number of polymer chains | 3 |
| Total formula weight | 57169.08 |
| Authors | Nelson, C.A.,Fremont, D.H. (deposition date: 2001-08-23, release date: 2001-09-12, Last modification date: 2023-08-16) |
| Primary citation | Lam, J.,Nelson, C.A.,Ross, F.P.,Teitelbaum, S.L.,Fremont, D.H. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity J.Clin.Invest., 108:971-979, 2001 Cited by PubMed Abstract: RANK, the receptor activator of NF-kappaB, and its ligand RANKL (initially termed TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair that govern the development and function of osteoclasts, lymphoid tissue, and mammary epithelium. While TNF family cytokines share a common structural scaffold, individual receptor-ligand pairs associate with high specificity. Given the low level of amino acid conservation among members of the TNF superfamily, the means by which these molecules achieve specificity cannot be completely understood without knowledge of their three-dimensional structures. To determine the elements of RANKL that mediate RANK activation, we have crystallized the ectodomain of murine RANKL and solved its structure to a resolution of 2.6 A. RANKL self-associates as a homotrimer with four unique surface loops that distinguish it from other TNF family cytokines. Mutagenesis of selected residues in these loops significantly modulates RANK activation, as evidenced by in vitro osteoclastogenesis, thereby establishing their necessity in mediating the biological activities of RANKL. Such structural determinants of RANKL-RANK specificity may be of relevance in the pharmacologic design of compounds to ameliorate osteopenic disorders of bone. PubMed: 11581298DOI: 10.1172/JCI200113890 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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