title: Structure and dimerization of a soluble form of B7-1.
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.
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, The University of Oxford, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Ikemizu
authors.forename: R J
authors.initials: RJ
authors.lastname: Gilbert
authors.forename: J A
authors.initials: JA
authors.lastname: Fennelly
authors.forename: A V
authors.initials: AV
authors.lastname: Collins
authors.forename: K
authors.initials: K
authors.lastname: Harlos
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
authors.forename: D I
authors.initials: DI
authors.lastname: Stuart
authors.forename: S J
authors.initials: SJ
authors.lastname: Davis
mesh_terms: 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
chemical_list: D018122:B7-1 Antigen; D007146:Immunoglobulin lambda-Chains; D008024:Ligands; D011993:Recombinant Fusion Proteins