View source for 8igt


==Crystal Structure of Intracellular B30.2 Domain of BTN2A1==
<StructureSection load='8igt' size='340' side='right'caption='[[8igt]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8igt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IGT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.56&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8igt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8igt OCA], [https://pdbe.org/8igt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8igt RCSB], [https://www.ebi.ac.uk/pdbsum/8igt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8igt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BT2A1_HUMAN BT2A1_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In both cancer and infections, diseased cells are presented to human Vgamma9Vdelta2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A1(1-4). Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vgamma9Vdelta2 T cell activation. Analyses using structure-based molecular-dynamics simulations, (19)F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated gammadelta T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human gammadelta T cell function.

Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vgamma9Vdelta2 T cells.,Yuan L, Ma X, Yang Y, Qu Y, Li X, Zhu X, Ma W, Duan J, Xue J, Yang H, Huang JW, Yi S, Zhang M, Cai N, Zhang L, Ding Q, Lai K, Liu C, Zhang L, Liu X, Yao Y, Zhou S, Li X, Shen P, Chang Q, Malwal SR, He Y, Li W, Chen C, Chen CC, Oldfield E, Guo RT, Zhang Y Nature. 2023 Sep;621(7980):840-848. doi: 10.1038/s41586-023-06525-3. Epub 2023 , Sep 6. PMID:37674084<ref>PMID:37674084</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8igt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cai NN]]
[[Category: Chen CC]]
[[Category: Guo RT]]
[[Category: Li X]]
[[Category: Yang YY]]
[[Category: Yuan LJ]]
[[Category: Zhang YH]]