Publication Date:
2000-10-29
Description:
The effective regulation of T cell responses is dependent on opposing signals transmitted through two related cell-surface receptors, CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Dimerization of CTLA-4 is required for the formation of high-avidity complexes with B7 ligands and for transmission of signals that attenuate T cell activation. We determined the crystal structure of the extracellular portion of CTLA-4 to 2.0 angstrom resolution. CTLA-4 belongs to the immunoglobulin superfamily and displays a strand topology similar to Valpha domains, with an unusual mode of dimerization that places the B7 binding sites distal to the dimerization interface. This organization allows each CTLA-4 dimer to bind two bivalent B7 molecules and suggests that a periodic arrangement of these components within the immunological synapse may contribute to the regulation of T cell responsiveness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ostrov, D A -- Shi, W -- Schwartz, J C -- Almo, S C -- Nathenson, S G -- AI07289/AI/NIAID NIH HHS/ -- AI42970/AI/NIAID NIH HHS/ -- CA09173/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Oct 27;290(5492):816-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11052947" target="_blank"〉PubMed〈/a〉
Keywords:
Abatacept
;
Amino Acid Sequence
;
Animals
;
Antigen-Presenting Cells/immunology
;
Antigens, CD
;
Antigens, CD28/immunology/metabolism
;
Antigens, CD80/chemistry/metabolism
;
Antigens, Differentiation/*chemistry/*immunology/metabolism
;
CTLA-4 Antigen
;
Crystallography, X-Ray
;
Dimerization
;
Hydrogen Bonding
;
*Immunoconjugates
;
Ligands
;
Lymphocyte Activation
;
Mice
;
Models, Molecular
;
Molecular Sequence Data
;
Protein Binding
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Receptors, Antigen, T-Cell/metabolism
;
Signal Transduction
;
T-Lymphocytes/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
