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

Article

关键词: TUMOR-NECROSIS-FACTOR;    B-CELL MATURATION;    CRYSTAL-STRUCTURE;    AUTOIMMUNE-DISEASE;    LYMPHOCYTE STIMULATOR;    BAFF;    TACI;    BLYS;    APRIL;    BCMA;   

DOI  :  10.1038/nature01543

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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