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| | ==Crystal Structure of the Human BTN3A1 Ectodomain in Complex with the 20.1 Single Chain Antibody== | | ==Crystal Structure of the Human BTN3A1 Ectodomain in Complex with the 20.1 Single Chain Antibody== |
| - | <StructureSection load='4f9l' size='340' side='right' caption='[[4f9l]], [[Resolution|resolution]] 3.14Å' scene=''> | + | <StructureSection load='4f9l' size='340' side='right'caption='[[4f9l]], [[Resolution|resolution]] 3.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4f9l]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F9L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F9L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f9l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F9L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><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]), IgG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4f9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f9l OCA], [https://pdbe.org/4f9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f9l RCSB], [https://www.ebi.ac.uk/pdbsum/4f9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f9l ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f9l OCA], [http://pdbe.org/4f9l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f9l RCSB], [http://www.ebi.ac.uk/pdbsum/4f9l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f9l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Adams, E J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bonneville, M]] | + | [[Category: Adams EJ]] |
| - | [[Category: Harly, C]] | + | [[Category: Bonneville M]] |
| - | [[Category: Nedellec, S]] | + | [[Category: Harly C]] |
| - | [[Category: Olive, D]] | + | [[Category: Nedellec S]] |
| - | [[Category: Palakodeti, A]] | + | [[Category: Olive D]] |
| - | [[Category: Sandstrom, A]] | + | [[Category: Palakodeti A]] |
| - | [[Category: Scotet, E]] | + | [[Category: Sandstrom A]] |
| - | [[Category: Sundaresan, L]] | + | [[Category: Scotet E]] |
| - | [[Category: B7 superfamily]]
| + | [[Category: Sundaresan L]] |
| - | [[Category: Butyrophilin]]
| + | |
| - | [[Category: Cd277]]
| + | |
| - | [[Category: Immune system]]
| + | |
| 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
Human Vgamma9Vdelta2 T cells are well known for their rapid and potent response to infection and tumorigenesis when in the presence of endogenous or exogenous phosphoisoprenoids. However, the molecular mechanisms behind the activation of this gammadelta T cell population remains unclear. Evidence pointing to a role for the CD277/butyrophilin-3 (BTN3A) molecules in this response led us to investigate the structures of these molecules and their modifications upon binding to an agonist antibody (20.1) that mimics phosphoisoprenoid-mediated Vgamma9Vdelta2 activation and an antagonist antibody (103.2) that inhibits this reactivity. We find that the three BTN3A isoforms: BTN3A1, BTN3A2, and BTN3A3, have high structural homology to the B7 superfamily of proteins and exist as V-shaped homodimers in solution, associating through the membrane proximal C-type Ig domain. The 20.1 and 103.2 antibodies bind to separate epitopes on the BTN3A Ig-V domain with high affinity but likely with different valencies based on their binding orientation. These structures directly complement functional studies of this system that demonstrate that BTN3A1 is necessary for Vgamma9Vdelta2 activation and begin to unravel the extracellular events that occur during stimulation through the Vgamma9Vdelta2 T cell receptor.
The molecular basis for modulation of human Vgamma9Vdelta2 T cell responses by CD277/butyrophilin-3 (BTN3A)-specific antibodies.,Palakodeti A, Sandstrom A, Sundaresan L, Harly C, Nedellec S, Olive D, Scotet E, Bonneville M, Adams EJ J Biol Chem. 2012 Sep 21;287(39):32780-90. Epub 2012 Jul 30. PMID:22846996[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ 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
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