title: The structure of the CD3ζζ transmembrane dimer in lipid bilayers.
abstract: Virtually every aspect of the human adaptive immune response is controlled by T cells. The T cell receptor (TCR) complex is responsible for the recognition of foreign peptide sequences, forming the initial step in the elimination of germ-infected cells. The recognition leads to an extracellular conformational change that is transmitted intracellularly through the Cluster of Differentiation 3 (CD3) subunits of the TCR-CD3 complex. Here we address the interplay between the disulfide-linked CD3ζζ dimer, an essential signaling component of the TCR-CD3 complex, and its lipidic environment. The disulfide bond formation requires the absolute presence of a nearby conserved aspartic acid, a fact that has mystified the scientific community. We use atomistic simulation methods to demonstrate that the conserved aspartic acid pair of the CD3ζζ dimer leads to a deformation of the membrane. This deformation changes the local environment of the cysteines and promotes disulfide bond formation. We also investigate the role of a conserved Tyr, highlighting its possible role in the interaction with other transmembrane components of the TCR-CD3 complex.
authors: Department of Biochemistry & Biocenter Oulu, University of Oulu, Oulu 90014, Finland.
authors: Satyan
authors: S
authors: Sharma
authors: Interdisciplinary Research Institute, CNRS USR3078, 50 avenue de Halley, F-59658 Villeneuve d'Ascq, France.
authors: Marc F
authors: MF
authors: Lensink
authors: Department of Biochemistry & Biocenter Oulu, University of Oulu, Oulu 90014, Finland. Electronic address: Andre.Juffer@oulu.fi.
authors: André H
authors: AH
authors: Juffer
mesh_terms: D017252:CD3 Complex / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D017252:CD3 Complex; D008051:Lipid Bilayers
keywords: CD3ζζ transmembrane domain; Molecular dynamics; T cell receptor; TCR–CD3 complex