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5hm7

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The Intracellular domain of Butyrophilin 3A1 protein

Structural highlights

5hm7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.93Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 respond to microbial infections as well as certain types of tumors. The key initiators of Vgamma9Vdelta2 activation are small, pyrophosphate-containing molecules called phosphoantigens (pAgs) that are present in infected cells or accumulate intracellularly in certain tumor cells. Recent studies demonstrate that initiation of the Vgamma9Vdelta2 T cell response begins with sensing of pAg via the intracellular domain of the butyrophilin 3A1 (BTN3A1) molecule. However, it is unknown how downstream events can ultimately lead to T cell activation. Here, using NMR spectrometry and molecular dynamics (MD) simulations, we characterize a global conformational change in the B30.2 intracellular domain of BTN3A1 induced by pAg binding. We also reveal by crystallography two distinct dimer interfaces in the BTN3A1 full-length intracellular domain, which are stable in MD simulations. These interfaces lie in close proximity to the pAg-binding pocket and contain clusters of residues that experience major changes of chemical environment upon pAg binding. This suggests that pAg binding disrupts a preexisting conformation of the BTN3A1 intracellular domain. Using a combination of biochemical, structural, and cellular approaches we demonstrate that the extracellular domains of BTN3A1 adopt a V-shaped conformation at rest, and that locking them in this resting conformation without perturbing their membrane reorganization properties diminishes pAg-induced T cell activation. Based on these results, we propose a model in which a conformational change in BTN3A1 is a key event of pAg sensing that ultimately leads to T cell activation.

Phosphoantigen-induced conformational change of butyrophilin 3A1 (BTN3A1) and its implication on Vgamma9Vdelta2 T cell activation.,Gu S, Sachleben JR, Boughter CT, Nawrocka WI, Borowska MT, Tarrasch JT, Skiniotis G, Roux B, Adams EJ Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7311-E7320. doi:, 10.1073/pnas.1707547114. Epub 2017 Aug 14. PMID:28807997^[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
↑ Gu S, Sachleben JR, Boughter CT, Nawrocka WI, Borowska MT, Tarrasch JT, Skiniotis G, Roux B, Adams EJ. Phosphoantigen-induced conformational change of butyrophilin 3A1 (BTN3A1) and its implication on Vgamma9Vdelta2 T cell activation. Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7311-E7320. doi:, 10.1073/pnas.1707547114. Epub 2017 Aug 14. PMID:28807997 doi:http://dx.doi.org/10.1073/pnas.1707547114

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5hm7"

Categories: Homo sapiens | Large Structures | Adams EJ | Gu S

@@ Line 3: / Line 3: @@
 <StructureSection load='5hm7' size='340' side='right'caption='[[5hm7]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hm7]] is a 2 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=5HM7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HM7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hm7]] is a 2 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=5HM7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HM7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BTN3A1, BTF5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=5hm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hm7 OCA], [http://pdbe.org/5hm7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hm7 RCSB], [http://www.ebi.ac.uk/pdbsum/5hm7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hm7 ProSAT]</span></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=5hm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hm7 OCA], [https://pdbe.org/5hm7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hm7 RCSB], [https://www.ebi.ac.uk/pdbsum/5hm7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hm7 ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Adams, E J]]
+[[Category: Adams EJ]]
-[[Category: Gu, S]]
+[[Category: Gu S]]
-[[Category: Immune system]]
-[[Category: Immunological protein]]
-[[Category: Intracellular domain]]

5hm7

From Proteopedia

Current revision

The Intracellular domain of Butyrophilin 3A1 protein

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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