Ligand-receptor binding revealed by the TNF family member TALL-1.

Journal Article · Thu May 01 04:00:00 EDT 2003 · Nature

DOI:https://doi.org/10.1038/nature01543· OSTI ID:961323

Liu, Y F; Hong, X; Kappler, J; Jiang, L; Zhang, R G; Xu, L G; Pan, C -H; Martin, W E; Murphy, R C; Shu, H -B; Dai, S D; Zhang, G Y

The tumour necrosis factor (TNF) ligand TALL-1 and its cognate receptors, BCMA, TACI and BAFF-R, were recently identified as members of the TNF superfamily, which are essential factors contributing to B-cell maturation. The functional, soluble fragment of TALL-1 (sTALL-1) forms a virus-like assembly for its proper function. Here we determine the crystal structures of sTALL-1 complexed with the extracellular domains of BCMA and BAFF-R at 2.6 and 2.5 {angstrom}, respectively. The single cysteine-rich domain of BCMA and BAFF-R both have saddle-like architectures, which sit on the horseback-like surface formed by four coil regions on each individual sTALL-1 monomer. Three novel structural modules, D2, X2 and N, were revealed from the current structures. Sequence alignments, structural modelling and mutagenesis revealed that one disulphide bridge in BAFF-R is critical for determining the binding specificity of the extracellular domain eBAFF-R to TALL-1 instead of APRIL, a closely related ligand of TALL-1, which was confirmed by binding experiments in vitro.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: NIH
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 961323
• Report Number(s): ANL/BIO/JA-46622
• Journal Information: Nature, Journal Name: Nature Journal Issue: 6935 ; May 1, 2003 Vol. 423
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
IN VITRO
LIGANDS
MUTAGENESIS
NECROSIS
RECEPTORS
RESPONSE MODIFYING FACTORS
SPECIFICITY
SURFACES