1I85

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

Summary for 1I85

• Entry DOI: 10.2210/pdb1i85/pdb
• Descriptor: T LYMPHOCYTE ACTIVATION ANTIGEN CD86, CYTOTOXIC T-LYMPHOCYTE-ASSOCIATED PROTEIN 4 (2 entities in total)
• Functional Keywords: ig v-type domain, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P42081 P16410
• Total number of polymer chains: 4
• Total formula weight: 52719.94

Authors

Schwartz, J.-C.D.,Zhang, X.,Fedorov, A.A.,Nathenson, S.G.,Almo, S.C. (deposition date: 2001-03-12, release date: 2001-04-04, Last modification date: 2024-11-13)

Primary citation

Schwartz, J.C.,Zhang, X.,Fedorov, A.A.,Nathenson, S.G.,Almo, S.C.
Structural basis for co-stimulation by the human CTLA-4/B7-2 complex.
Nature, 410:604-608, 2001

PubMed Abstract: 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.

PubMed: 11279501
DOI: 10.1038/35069112

Experimental method

X-RAY DIFFRACTION (3.2 Å)