1OQE | pdb_00001oqe

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

(2003) Nature&nbsp423: 49-56

• PubMed:&nbsp12721620&nbspSearch on PubMed
• DOI:&nbsphttps://doi.org/10.1038/nature01543
• Primary Citation of Related Structures: &nbsp
  1OQD, 1OQE


• PubMed Abstract:&nbsp
  

  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 A, 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.

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Organizational Affiliation:&nbsp

Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.