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| {{STRUCTURE_1i85| PDB=1i85 | SCENE= }} | | {{STRUCTURE_1i85| PDB=1i85 | SCENE= }} |
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| '''CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX'''
| | ===CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11279501}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11279501 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11279501}} |
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| ==Disease== | | ==Disease== |
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| [[Category: Zhang, X.]] | | [[Category: Zhang, X.]] |
| [[Category: Ig v-type domain]] | | [[Category: Ig v-type domain]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:41:38 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:34:00 2008'' |