Structure and dimerization of a soluble form of B7-1

Ikemizu S, Gilbert RJ, Fennelly JA, Collins AV, Harlos K, Jones EY, Stuart DI, Davis SJ. (2000), Immunity. 12, 51-60

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.

Key figure: Structure of the sB7-1 Homodimer Observed in the Crystal Lattice

(A) Two orthogonal views of the GRASP surface of the homodimer showing the location of residues whose mutation to alanine disrupts (magenta) or has no effect (cyan) on binding. Putative N-glycosylation sites are colored green. (B) The GRASP surfaces of amino acids involved in forming the dimer are colored red. The view is identical to the right-hand panel in (A) but with the front copy of sB7-1 removed. (C) Details of the residues at the dimer interface are shown in ball-and-stick format viewed as in the left-hand panel of (A). (D) The homodimer is shown with either oligomannose, bi-, or triantennary N-glycans modeled at each of the potential glycosylation sites.