1i85
CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX
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OverviewOverview
Regulation of T-cell activity is dependent on antigen-independent, co-stimulatory signals provided by the disulphide-linked homodimeric, T-cell surface receptors, CD28 and CTLA-4 (ref. 1). Engagement of CD28, with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a, stimulatory signal for T-cell activation, whereas subsequent engagement of, CTLA-4 with these same ligands results in attenuation of the response., Given their central function in immune modulation, CTLA-4- and, CD28-associated signalling pathways are primary therapeutic targets for, preventing autoimmune disease, graft versus host disease, graft rejection, and promoting tumour immunity. However, little is known about the, cell-surface organization of these receptor/ligand complexes and the, structural basis for signal transduction. Here we report the 3.2-A, resolution structure of the complex between the disulphide-linked, homodimer of human CTLA-4 and the receptor-binding domain of human B7-2., The unusual dimerization properties of both CTLA-4 and B7-2 place their, respective ligand-binding sites distal to the dimer interface in each, molecule and promote the formation of an alternating arrangement of, bivalent CTLA-4 and B7-2 dimers that extends throughout the crystal., Direct observation of this CTLA-4/B7-2 network provides a model for the, periodic organization of these molecules within the immunological synapse, and suggests a distinct mechanism for signalling by dimeric cell-surface, receptors.
DiseaseDisease
Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[123890], Diabetes mellitus, insulin-dependent, susceptibility to OMIM:[123890], Graves disease, susceptibility to OMIM:[123890], Hypothyroidism, autoimmune OMIM:[123890]
About this StructureAbout this Structure
1I85 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for co-stimulation by the human CTLA-4/B7-2 complex., Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC, Nature. 2001 Mar 29;410(6828):604-8. PMID:11279501
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