title: Cooperativity between T cell receptor complexes revealed by conformational mutants of CD3epsilon.
abstract: The CD3epsilon subunit of the T cell receptor (TCR) complex undergoes a conformational change upon ligand binding that is thought to be important for the activation of T cells. To study this process, we built a molecular dynamics model of the transmission of the conformational change within the ectodomains of CD3. The model showed that the CD3 dimers underwent a stiffening effect that was funneled to the base of the CD3epsilon subunit. Mutation of two relevant amino acid residues blocked transmission of the conformational change and the differentiation and activation of T cells. Furthermore, this inhibition occurred even in the presence of excess endogenous CD3epsilon subunits. These results emphasize the importance of the conformational change in CD3epsilon for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes.
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
authors: Nuria
authors: N
authors: Martínez-Martín
authors: Ruth M
authors: RM
authors: Risueño
authors: Antonio
authors: A
authors: Morreale
authors: Irene
authors: I
authors: Zaldívar
authors: Elena
authors: E
authors: Fernández-Arenas
authors: Fernando
authors: F
authors: Herranz
authors: Angel R
authors: AR
authors: Ortiz
authors: Balbino
authors: B
authors: Alarcón
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C485468:Cd3e protein, mouse; D050505:Mutant Proteins; D011948:Receptors, Antigen, T-Cell