Structure and dimerization of a soluble form of B7-1

Immunity. 2000 Jan;12(1):51-60. doi: 10.1016/s1074-7613(00)80158-2.

Abstract

B7-1 (CD80) and B7-2 (CD86) are glycoproteins expressed on antigen-presenting cells. The binding of these molecules to the T cell homodimers CD28 and CTLA-4 (CD152) generates costimulatory and inhibitory signals in T cells, respectively. The crystal structure of the extracellular region of B7-1 (sB7-1), solved to 3 A resolution, consists of a novel combination of two Ig-like domains, one characteristic of adhesion molecules and the other previously seen only in antigen receptors. In the crystal lattice, sB7-1 unexpectedly forms parallel, 2-fold rotationally symmetric homodimers. Analytical ultracentrifugation reveals that sB7-1 also dimerizes in solution. The structural data suggest a mechanism whereby the avidity-enhanced binding of B7-1 and CTLA-4 homodimers, along with the relatively high affinity of these interactions, favors the formation of very stable inhibitory signaling complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B7-1 Antigen / chemistry*
  • B7-1 Antigen / genetics
  • CHO Cells
  • Cricetinae
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Immunoglobulin lambda-Chains / chemistry
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Protein Conformation*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Sequence Homology, Amino Acid
  • Solubility

Substances

  • B7-1 Antigen
  • Immunoglobulin lambda-Chains
  • Ligands
  • Recombinant Fusion Proteins

Associated data

  • PDB/1DR9