1I8L

HUMAN B7-1/CTLA-4 CO-STIMULATORY COMPLEX

Summary for 1I8L

• Entry DOI: 10.2210/pdb1i8l/pdb
• Related: 1DR9
• Descriptor: T LYMPHOCYTE ACTIVATION ANTIGEN CD80, CYTOTOXIC T-LYMPHOCYTE PROTEIN 4, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: receptors, inhibitory complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 79086.72

Authors

Stamper, C.C.,Somers, W.S.,Mosyak, L. (deposition date: 2001-03-14, release date: 2001-04-04, Last modification date: 2024-11-20)

Primary citation

Stamper, C.C.,Zhang, Y.,Tobin, J.F.,Erbe, D.V.,Ikemizu, S.,Davis, S.J.,Stahl, M.L.,Seehra, J.,Somers, W.S.,Mosyak, L.
Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses.
Nature, 410:608-611, 2001

PubMed Abstract: Optimal immune responses require both an antigen-specific and a co-stimulatory signal. The shared ligands B7-1 and B7-2 on antigen-presenting cells deliver the co-stimulatory signal through CD28 and CTLA-4 on T cells. Signalling through CD28 augments the T-cell response, whereas CTLA-4 signalling attenuates it. Numerous animal studies and recent clinical trials indicate that manipulating these interactions holds considerable promise for immunotherapy. With the consequences of these signals well established, and details of the downstream signalling events emerging, understanding the molecular nature of these extracellular interactions becomes crucial. Here we report the crystal structure of the human CTLA-4/B7-1 co-stimulatory complex at 3.0 A resolution. In contrast to other interacting cell-surface molecules, the relatively small CTLA-4/B7-1 binding interface exhibits an unusually high degree of shape complementarity. CTLA-4 forms homodimers through a newly defined interface of highly conserved residues. In the crystal lattice, CTLA-4 and B7-1 pack in a strikingly periodic arrangement in which bivalent CTLA-4 homodimers bridge bivalent B7-1 homodimers. This zipper-like oligomerization provides the structural basis for forming unusually stable signalling complexes at the T-cell surface, underscoring the importance of potent inhibitory signalling in human immune responses.

PubMed: 11279502
DOI: 10.1038/35069118

Experimental method

X-RAY DIFFRACTION (3 Å)