4n7i

Crystal Structure of Intracellular B30.2 Domain of BTN3A1

spinqualitylabelsall models 4n7i, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4n7i is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, CL, GOL, MG Related: 4n7u Gene: BTF5, BTN3A1 (HUMAN) Resources: FirstGlance, OCA, RCSB, PDBsum Function [BT3A1_HUMAN] Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate. Publication Abstract from PubMed In humans, Vgamma9Vdelta2 T cells detect tumor cells and microbial infections, including Mycobacterium tuberculosis, through recognition of small pyrophosphate containing organic molecules known as phosphoantigens (pAgs). Key to pAg-mediated activation of Vgamma9Vdelta2 T cells is the butyrophilin 3A1 (BTN3A1) protein that contains an intracellular B30.2 domain critical to pAg reactivity. Here, we have demonstrated through structural, biophysical, and functional approaches that the intracellular B30.2 domain of BTN3A1 directly binds pAg through a positively charged surface pocket. Charge reversal of pocket residues abrogates binding and Vgamma9Vdelta2 T cell activation. We have also identified a gain-of-function mutation within this pocket that, when introduced into the B30.2 domain of the nonstimulatory BTN3A3 isoform, transfers pAg binding ability and Vgamma9Vdelta2 T cell activation. These studies demonstrate that internal sensing of changes in pAg metabolite concentrations by BTN3A1 molecules is a critical step in Vgamma9Vdelta2 T cell detection of infection and tumorigenesis. The Intracellular B30.2 Domain of Butyrophilin 3A1 Binds Phosphoantigens to Mediate Activation of Human Vgamma9Vdelta2 T Cells.,Sandstrom A, Peigne CM, Leger A, Crooks JE, Konczak F, Gesnel MC, Breathnach R, Bonneville M, Scotet E, Adams EJ Immunity. 2014 Apr 17;40(4):490-500. doi: 10.1016/j.immuni.2014.03.003. Epub 2014, Apr 3. PMID:24703779 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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