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CD3 EPSILON AND DELTA ECTODOMAIN FRAGMENT COMPLEX IN SINGLE-CHAIN CONSTRUCTCD3 EPSILON AND DELTA ECTODOMAIN FRAGMENT COMPLEX IN SINGLE-CHAIN CONSTRUCT
Structural highlights
FunctionCD3D_SHEEP Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly. Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells.[UniProtKB:P04234]CD3E_MOUSE The CD3 complex mediates signal transduction. 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 PubMedInvariant CD3 subunit dimers (CD3epsilongamma, CD3epsilondelta, and CD3zetazeta) are the signaling components of the alphabeta T cell receptor (TCR). The recently solved structure of murine CD3epsilongamma revealed a unique side-to-side interface and central beta-sheets conjoined between the two C2-set Ig-like ectodomains, with the pairing of the parallel G strands implying a potential concerted piston-type movement for signal transduction. Although CD3gamma and CD3delta each dimerize with CD3epsilon, there are differential CD3 subunit requirements for receptor assembly and signaling among T lineage subpopulations, presumably mandated by structural differences. Here we present the solution structure of the heterodimeric CD3epsilondelta complex. Whereas the CD3epsilon subunit conformation is virtually identical to that in CD3epsilongamma, the CD3delta ectodomain adopts a C1-set Ig fold, with a narrower GFC front face beta-sheet that is more parallel to the ABED back face than those beta-sheets in CD3epsilon and CD3gamma. The dimer interface between CD3delta and CD3epsilon is highly conserved among species and of similar character to that in CD3epsilongamma. Glycosylation sites in CD3delta are arranged such that the glycans may point away from the membrane, consistent with a model of TCR assembly that allows the CD3delta chain to be in close contact with the TCR alpha-chain. This and many other structural and biological features provide a basis for modeling putative TCR/CD3 extracellular domain associations. The fact that the two clusters of transmembrane helices, namely, the three CD3epsilon-CD3gamma-TCRbeta segments and the five CD3epsilon-CD3delta-TCRalpha-CD3zeta-CD3zeta segments, are presumably centered beneath the G strand-paired CD3 heterodimers has important implications for TCR signaling. Solution structure of the CD3epsilondelta ectodomain and comparison with CD3epsilongamma as a basis for modeling T cell receptor topology and signaling.,Sun ZY, Kim ST, Kim IC, Fahmy A, Reinherz EL, Wagner G Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16867-72. Epub 2004 Nov 19. PMID:15557001[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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