Binding Stoichiometry of the Cytotoxic T Lymphocyte-associated Molecule-4 (CTLA-4)

Autor:	Gina Leytze, Steven G. Nadler, Alison R. Malacko, Peter S. Linsley, Helios T. Leung, Jeff Bradshaw, Mark R. Stebbins, Robert J. Peach, Hans Marquardt, William E. Brady, Shyh Yu Shaw, Jürgen Bajorath, Julie Rogers
Rok vydání:	1995
Předmět:	CD86 Chemistry Stereochemistry Protein subunit Binding protein T-cell receptor Cooperative binding hemic and immune systems chemical and pharmacologic phenomena Cell Biology Plasma protein binding Biochemistry biological factors Binding site Molecular Biology Cysteine
Zdroj:	Journal of Biological Chemistry. 270:15417-15424
ISSN:	0021-9258
DOI:	10.1074/jbc.270.25.15417
Popis:	CD28 and CTLA-4 are homologous T cell receptors of the immunoglobulin (Ig) superfamily, which bind B7 molecules (CD80 and CD86) on antigen-presenting cells and transmit important costimulatory signals during T cell activation. Here we have investigated the subunit structure of CTLA-4 and the stoichiometry of its binding to B7 molecules. We demonstrate CTLA-4 is a homodimer interconnected by one disulfide bond in the extracellular domain at cysteine residue 120. Each monomeric polypeptide chain of CTLA-4 contains a high affinity binding site for B7 molecules; soluble CTLA-4 and CD86 form complexes containing equimolar amounts of monomeric CTLA-4 and CD86 (i.e. a 2:2 molecular complex). Thus, CTLA-4 and probably CD28 have a receptor structure consisting of preexisting covalent homodimers with two binding sites. Dimerization of CTLA-4 and CD28 is not required for B7 binding, nor is it sufficient to trigger signaling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::c68c4aa830c35118d5d4e5df81b8543e https://doi.org/10.1074/jbc.270.25.15417