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

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 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.

journal_name

Nature

journal_title

Nature

authors

Liu Y,Hong X,Kappler J,Jiang L,Zhang R,Xu L,Pan CH,Martin WE,Murphy RC,Shu HB,Dai S,Zhang G

doi

10.1038/nature01543

keywords:

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

49-56

issue

6935

eissn

0028-0836

issn

1476-4687

pii

nature01543

journal_volume

423

pub_type

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