1hxm
From Proteopedia
Crystal Structure of a Human Vgamma9/Vdelta2 T Cell Receptor
Structural highlights
FunctionTRDC_HUMAN Constant region of T cell receptor (TR) delta chain that participates in the antigen recognition (PubMed:24600447). Gamma-delta TRs recognize a variety of self and foreign non-peptide antigens frequently expressed at the epithelial boundaries between the host and external environment, including endogenous lipids presented by MH-like protein CD1D and phosphoantigens presented by butyrophilin-like molecule BTN3A1. Upon antigen recognition induces rapid, innate-like immune responses involved in pathogen clearance and tissue repair (PubMed:23348415, PubMed:28920588). Binding of gamma-delta TR complex to antigen triggers phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the CD3 chains by the LCK and FYN kinases, allowing the recruitment, phosphorylation, and activation of ZAP70 that facilitates phosphorylation of the scaffolding proteins LCP2 and LAT. This lead to the formation of a supramolecular signalosome that recruits the phospholipase PLCG1, resulting in calcium mobilization and ERK activation, ultimately leading to T cell expansion and differentiation into effector cells (PubMed:25674089). Gamma-delta TRs are produced through somatic rearrangement of a limited repertoire of variable (V), diversity (D), and joining (J) genes. The potential diversity of gamma-delta TRs is conferred by the unique ability to rearrange (D) genes in tandem and to utilize all three reading frames. The combinatorial diversity is considerably increased by the sequence exonuclease trimming and random nucleotide (N) region additions which occur during the V-(D)-J rearrangements (PubMed:24387714).[1] [2] [3] [4] [5] 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 PubMedT-cell antigen receptors composed of gamma and delta polypeptide chains (gammadelta TCRs) can directly recognize antigens in the form of intact proteins or non-peptide compounds, unlike alphabeta TCRs, which recognize antigens bound to major histocompatibility complex molecules (MHC). About 5% of peripheral blood T cells bear gammadelta TCRs, most of which recognize non-peptide phosphorylated antigens. Here we describe the 3.1 A resolution structure of a human gammadelta TCR from a T-cell clone that is phosphoantigen-reactive. The orientation of the variable (V) and constant (C) regions of the gammadelta TCR is unique when compared with alphabeta TCRs or antibodies, and results from an unusually small angle between the Vgamma and Cgamma domains. The complementarity-determining regions (CDRs) of the V domains exhibit a chemically reasonable binding site for phosphorylated antigens, providing a possible explanation for the canonical usage of the Vgamma9 and Vdelta2 gene segments by phosphoantigen-reactive receptors. Although the gammadelta TCR V domains are similar in overall structure to those of alphabeta TCRs, gammadelta TCR C domains are markedly different. Structural differences in Cgamma and Cdelta, and in the location of the disulphide bond between them, may enable gammadelta TCRs to form different recognition/signalling complexes than alphabeta TCRs. Structure of a human gammadelta T-cell antigen receptor.,Allison TJ, Winter CC, Fournie JJ, Bonneville M, Garboczi DN Nature. 2001 Jun 14;411(6839):820-4. PMID:11459064[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations 63 reviews cite this structure No citations found See AlsoReferences
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