1i85

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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 11279501 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11279501}}
==Disease==
==Disease==
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[[Category: Zhang, X.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:34:00 2008''

Revision as of 07:34, 1 July 2008

Template:STRUCTURE 1i85

Contents

CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX

Template:ABSTRACT PUBMED 11279501

Disease

Known disease 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 Structure

1I85 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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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