4GIQ

Crystal Structure of mouse RANK bound to RANKL

4GIQ の概要

• エントリーDOI: 10.2210/pdb4giq/pdb
• 関連するPDBエントリー: 1D0G 1D4V 1JTZ 3k51 3me2 3ME4 3QBQ
• 分子名称: Tumor necrosis factor ligand superfamily member 11, Tumor necrosis factor receptor superfamily member 11A, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: rank, odfr, activation-induced cytokine-receptor, tnfrsf11a, rankl, opgl, tnf-like cytokine, cysteine-rich domain, jelly-roll fold, protein binding-protein binding complex, protein binding/protein binding
• 由来する生物種: Mus musculus (mouse); 詳細
• 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; Cell membrane ; Single-pass type I membrane protein : O35305
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38404.94

構造登録者

Nelson, C.A.,Wang, M.W.-H.,Fremont, D.H. (登録日: 2012-08-08, 公開日: 2012-10-24, 最終更新日: 2024-10-16)

主引用文献

Nelson, C.A.,Warren, J.T.,Wang, M.W.,Teitelbaum, S.L.,Fremont, D.H.
RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor.
Structure, 20:1971-1982, 2012

PubMed Abstract: Osteoprotegerin (OPG) and receptor activator of nuclear factor κB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with ∼500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis ∼150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.

PubMed: 23039992
DOI: 10.1016/j.str.2012.08.030

実験手法

X-RAY DIFFRACTION (2.7 Å)