Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands.
TALL-1/BAFF/BLyS was recently identified as a member of the tumor necrosis factor (TNF) ligand family. The crystal structure of the functional soluble TALL-1 (sTALL-1) has been determined at 3.0 A. sTALL-1 forms a virus-like assembly with 200 A diameter in the crystals, containing 60 sTALL-1 monomers. The cluster formation is mediated by a "flap" region of the sTALL-1 monomer. The virus-like assembly was also detected in solution using gel filtration and electron microscopy. Deletion of the flap region disrupted the formation of the virus-like assembly. The mutant sTALL-1 still bound its receptor but could not activate NF-kappaB and did not stimulate B lymphocyte proliferation. Finally, we found the virus-like cluster of sTALL-1 exists in physiological condition. We propose that this virus-like assembly of sTALL-1 is the functional unit for TALL-1 in vivo.
Liu
Yingfang
Y
National Jewish Medical and Research Center, Integrated Department of Immunology, Denver, CO 80206, USA.
Xu
Liangguo
L
Opalka
Natasha
N
Kappler
John
J
Shu
Hong Bing
HB
Zhang
Gongyi
G
D000595:Amino Acid Sequence; D053264:B-Cell Activating Factor; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D019065:Virus Assembly
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha