Structure and dimerization of a soluble form of B7-1.
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.
Ikemizu
S
S
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, The University of Oxford, United Kingdom.
Gilbert
R J
RJ
Fennelly
J A
JA
Collins
A V
AV
Harlos
K
K
Jones
E Y
EY
Stuart
D I
DI
Davis
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D018122:B7-1 Antigen / Q000737:chemistry* / Q000235:genetics; D016466:CHO Cells; D006224:Cricetinae; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D018122:B7-1 Antigen; D007146:Immunoglobulin lambda-Chains; D008024:Ligands; D011993:Recombinant Fusion Proteins