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| | ==Crystal Structure of Intracellular B30.2 Domain of BTN3A1== | | ==Crystal Structure of Intracellular B30.2 Domain of BTN3A1== |
| - | <StructureSection load='4n7i' size='340' side='right' caption='[[4n7i]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='4n7i' size='340' side='right'caption='[[4n7i]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4n7i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N7I OCA]. <br> | + | <table><tr><td colspan='2'>[[4n7i]] 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=4N7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N7I FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><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]] 1.4015Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n7u|4n7u]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BTF5, BTN3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4n7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7i OCA], [https://pdbe.org/4n7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n7i RCSB], [https://www.ebi.ac.uk/pdbsum/4n7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n7i ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
| + | </table> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n7i RCSB], [http://www.ebi.ac.uk/pdbsum/4n7i PDBsum]</span></td></tr>
| + | == Function == |
| - | <table> | + | [https://www.uniprot.org/uniprot/BT3A1_HUMAN 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.<ref>PMID:21113407</ref> <ref>PMID:21918970</ref> <ref>PMID:22767497</ref> <ref>PMID:22846996</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | 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<ref>PMID:24703779</ref> | | 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<ref>PMID:24703779</ref> |
| | | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4n7i" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Adams, E J.]] | + | [[Category: Large Structures]] |
| - | [[Category: Sandstrom, A.]] | + | [[Category: Adams EJ]] |
| - | [[Category: B30 2]] | + | [[Category: Sandstrom A]] |
| - | [[Category: Butyrophilin]]
| + | |
| - | [[Category: Cd277]]
| + | |
| - | [[Category: Pty/spry]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
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.[1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cubillos-Ruiz JR, Martinez D, Scarlett UK, Rutkowski MR, Nesbeth YC, Camposeco-Jacobs AL, Conejo-Garcia JR. CD277 is a negative co-stimulatory molecule universally expressed by ovarian cancer microenvironmental cells. Oncotarget. 2010 Sep;1(5):329-38. PMID:21113407
- ↑ Messal N, Mamessier E, Sylvain A, Celis-Gutierrez J, Thibult ML, Chetaille B, Firaguay G, Pastor S, Guillaume Y, Wang Q, Hirsch I, Nunes JA, Olive D. Differential role for CD277 as a co-regulator of the immune signal in T and NK cells. Eur J Immunol. 2011 Dec;41(12):3443-54. doi: 10.1002/eji.201141404. Epub 2011 Nov, 3. PMID:21918970 doi:10.1002/eji.201141404
- ↑ Harly C, Guillaume Y, Nedellec S, Peigne CM, Monkkonen H, Monkkonen J, Li J, Kuball J, Adams EJ, Netzer S, Dechanet-Merville J, Leger A, Herrmann T, Breathnach R, Olive D, Bonneville M, Scotet E. Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human gammadelta T-cell subset. Blood. 2012 Sep 13;120(11):2269-79. doi: 10.1182/blood-2012-05-430470. Epub 2012 , Jul 5. PMID:22767497 doi:10.1182/blood-2012-05-430470
- ↑ Palakodeti A, Sandstrom A, Sundaresan L, Harly C, Nedellec S, Olive D, Scotet E, Bonneville M, Adams EJ. The molecular basis for modulation of human Vgamma9Vdelta2 T cell responses by CD277/butyrophilin-3 (BTN3A)-specific antibodies. J Biol Chem. 2012 Sep 21;287(39):32780-90. Epub 2012 Jul 30. PMID:22846996 doi:10.1074/jbc.M112.384354
- ↑ Sandstrom A, Peigne CM, Leger A, Crooks JE, Konczak F, Gesnel MC, Breathnach R, Bonneville M, Scotet E, Adams EJ. The Intracellular B30.2 Domain of Butyrophilin 3A1 Binds Phosphoantigens to Mediate Activation of Human Vgamma9Vdelta2 T Cells. Immunity. 2014 Apr 17;40(4):490-500. doi: 10.1016/j.immuni.2014.03.003. Epub 2014, Apr 3. PMID:24703779 doi:http://dx.doi.org/10.1016/j.immuni.2014.03.003
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