Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation

Nat Struct Biol. 2003 May;10(5):342-8. doi: 10.1038/nsb925.

Abstract

B-cell activating factor (BAFF) is a key regulator of B-lymphocyte development. Its biological role is mediated by the specific receptors BCMA, TACI and BAFF-R. We have determined the crystal structure of the extracellular domain of BAFF-R bound to BAFF at a resolution of 3.3 A. The cysteine-rich domain (CRD) of the BAFF-R extracellular domain adopts a beta-hairpin structure and binds to the virus-like BAFF cage in a 1:1 molar ratio. The conserved DxL motif of BAFF-R is located on the tip of the beta-turn and is indispensable in the binding of BAFF. The crystal structure shows that a unique dimeric contact occurs between the BAFF-R monomers in the virus-like cage complex. The extracellular domain of TACI contains two CRDs, both of which contain the DxL motif. Modeling of TACI-BAFF complex suggests that both CDRs simultaneously interact with the BAFF dimer in the virus-like cage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Conserved Sequence
  • Crystallography, X-Ray
  • Humans
  • Immunoglobulin G / chemistry
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Receptors, Tumor Necrosis Factor / chemistry*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tumor Necrosis Factor-alpha / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Immunoglobulin G
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • TNFRSF13C protein, human
  • TNFSF13B protein, human
  • Tnfrsf13c protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor-alpha

Associated data

  • PDB/1OTZ