Abstract
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 Å, 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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Acknowledgements
We thank R. Zhao, O. Swartz and L. Halton for reading our manuscript; Z. Chen for Fig. 5f; M. Carson, S. R. Sprang, C. R. Mackay and J. Tschopp for their suggestions; the Howard Hughes Medical Institute, Zuckerman/Canyon Ranch and A. Lapporte for the support of our X-ray and computing facility; A. Joachimiak and SBC (ID-19) at APS for high-resolution data; and P. C. Marrack, J. D. Crapo, J. Cambier, X. Liu and other members at the National Jewish Medical and Research Center for support. S.H.B. is supported by an NIH grant and the Arthritis Foundation; Y.L. is supported partly by a Priscilla Campbell Memorial Fellowship; X.H. is supported partly by a Janet S. Lewald fellowship; G.Z. is supported by a PEW Scholar Award, a start-up fund from National Jewish Medical and Research Center and the Cancer League of Colorado, Inc.; P.M. and G.Z. are supported by NIH grants.
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Liu, Y., Hong, X., Kappler, J. et al. Ligand–receptor binding revealed by the TNF family member TALL-1. Nature 423, 49–56 (2003). https://doi.org/10.1038/nature01543
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DOI: https://doi.org/10.1038/nature01543
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