1nfd | pdb_00001nfd
AN ALPHA-BETA T CELL RECEPTOR (TCR) HETERODIMER IN COMPLEX WITH AN ANTI-TCR FAB FRAGMENT DERIVED FROM A MITOGENIC ANTIBODY
Structural highlights
FunctionTRAC_MOUSE Constant region of T cell receptor (TR) alpha chain. Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens. Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation. The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity.[UniProtKB:P01848] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEach T cell receptor (TCR) recognizes a peptide antigen bound to a major histocompatibility complex (MHC) molecule via a clonotypic alphabeta heterodimeric structure (Ti) non-covalently associated with the monomorphic CD3 signaling components. A crystal structure of an alphabeta TCR-anti-TCR Fab complex shows an Fab fragment derived from the H57 monoclonal antibody (mAb), interacting with the elongated FG loop of the Cbeta domain, situated beneath the Vbeta domain. This loop, along with the partially exposed ABED beta sheet of Cbeta, and glycans attached to both Cbeta and Calpha domains, forms a cavity of sufficient size to accommodate a single non-glycosylated Ig domain such as the CD3epsilon ectodomain. That this asymmetrically localized site is embedded within the rigid constant domain module has implications for the mechanism of signal transduction in both TCR and pre-TCR complexes. Furthermore, quaternary structures of TCRs vary significantly even when they bind the same MHC molecule, as manifested by a unique twisting of the V module relative to the C module. Atomic structure of an alphabeta T cell receptor (TCR) heterodimer in complex with an anti-TCR fab fragment derived from a mitogenic antibody.,Wang J, Lim K, Smolyar A, Teng M, Liu J, Tse AG, Liu J, Hussey RE, Chishti Y, Thomson CT, Sweet RM, Nathenson SG, Chang HC, Sacchettini JC, Reinherz EL EMBO J. 1998 Jan 2;17(1):10-26. PMID:9427737[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
