1JTZ

CRYSTAL STRUCTURE OF TRANCE/RANKL CYTOKINE.

1JTZ の概要

• エントリーDOI: 10.2210/pdb1jtz/pdb
• 分子名称: TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 11 (2 entities in total)
• 機能のキーワード: tumor necrosis factor superfamily member, jellyroll, beta-sandwich, cytokine
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: 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
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 57169.08

構造登録者

Nelson, C.A.,Fremont, D.H. (登録日: 2001-08-23, 公開日: 2001-09-12, 最終更新日: 2023-08-16)

主引用文献

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

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: 11581298
DOI: 10.1172/JCI200113890

実験手法

X-RAY DIFFRACTION (2.6 Å)