Crystal structure of the extracellular domain of mouse RANK ligand at 2.2-A resolution.
Bone remodeling involves the resorption of bone by osteoclasts and the synthesis of bone matrix by osteoblasts. Receptor activator of NF-kappa B ligand (RANKL, also known as ODF and OPGL), a member of the tumor necrosis factor (TNF) family, triggers osteoclastogenesis by forming a complex with its receptor, RANK. We have determined the crystal structure of the extracellular domain of mouse RANKL at 2.2-A resolution. The structure reveals that the RANKL extracellular domain is trimeric, which was also shown by analytical ultracentrifugation, and each subunit has a beta-strand jellyroll topology like the other members of the TNF family. A comparison of RANKL with TNF beta and TNF-related apoptosis-inducing ligand (TRAIL), whose structures were determined to be in the complex form with their respective receptor, reveals conserved and specific features of RANKL in the TNF superfamily and suggests the presence of key residues of RANKL for receptor binding.
Ito
Shuichiro
S
Biomedical Research Laboratories, Sankyo, Co., Ltd. 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan. shuici@shina.sanyko.co.jp
Wakabayashi
Kenji
K
Ubukata
Osamu
O
Hayashi
Shinko
S
Okada
Fumihiko
F
Hata
Tadashi
T
D000595:Amino Acid Sequence; D000818:Animals; D016723:Bone Remodeling; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008233:Lymphotoxin-alpha / Q000737:chemistry; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology; D053244:Osteoprotegerin; D010446:Peptide Fragments / Q000737:chemistry; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D006023:Glycoproteins; D008233:Lymphotoxin-alpha; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D010446:Peptide Fragments; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse