5lyg

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF INTRACELLULAR B30.2 DOMAIN OF BTN3A1 BOUND TO MALONATE

Structural highlights

5lyg is a 1 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 1.6Å
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 Vgamma9/Vdelta2 T-cells detect tumour cells and microbial infections by recognising small phosphorylated prenyl metabolites termed phosphoantigens (P-Ag). The type-1 transmembrane protein Butyrophilin 3A1 (BTN3A1) is critical to the P-Ag-mediated activation of Vgamma9/Vdelta2 T-cells, however, the molecular mechanisms involved in BTN3A1-mediated metabolite sensing are unclear, including how P-Ag are discriminated from non-antigenic small molecules. Here, we utilised NMR and X-ray crystallography to probe P-Ag sensing by BTN3A1. Whereas the BTN3A1 Immunoglobulin Variable domain failed to bind P-Ag, the intracellular B30.2 domain bound a range of negatively-charged small molecules, including P-Ag, in a positively-charged surface pocket. However, NMR chemical shift perturbations indicated BTN3A1 discriminated P-Ag from non-antigenic small molecules by their ability to induce a specific conformational change in the B30.2 domain that propagated from the P-Ag binding site to distal parts of the domain. These results suggest BTN3A1 selectively detects P-Ag intracellularly via a conformational antigenic sensor in its B30.2 domain, and have implications for rational design of antigens for Vgamma9/Vdelta2 -based T-cell immunotherapies.

BTN3A1 discriminates gammadelta T cell phosphoantigens from non-antigenic small molecules via a conformational sensor in its B30.2 domain.,Salim M, Knowles TJ, Baker AT, Davey MS, Jeeves M, Sridhar P, Wilkie J, Willcox CR, Kadri H, Taher TE, Vantourout P, Hayday A, Mehellou Y, Mohammed F, Willcox BE ACS Chem Biol. 2017 Sep 1. doi: 10.1021/acschembio.7b00694. PMID:28862425^[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
↑ Salim M, Knowles TJ, Baker AT, Davey MS, Jeeves M, Sridhar P, Wilkie J, Willcox CR, Kadri H, Taher TE, Vantourout P, Hayday A, Mehellou Y, Mohammed F, Willcox BE. BTN3A1 discriminates gammadelta T cell phosphoantigens from non-antigenic small molecules via a conformational sensor in its B30.2 domain. ACS Chem Biol. 2017 Sep 1. doi: 10.1021/acschembio.7b00694. PMID:28862425 doi:http://dx.doi.org/10.1021/acschembio.7b00694

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/5lyg"

@@ Line 3: / Line 3: @@
 <StructureSection load='5lyg' size='340' side='right'caption='[[5lyg]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5lyg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LYG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LYG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5lyg]] 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=5LYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LYG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 1.6&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lyg OCA], [http://pdbe.org/5lyg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lyg RCSB], [http://www.ebi.ac.uk/pdbsum/5lyg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lyg ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=5lyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lyg OCA], [https://pdbe.org/5lyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lyg RCSB], [https://www.ebi.ac.uk/pdbsum/5lyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lyg 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 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Baker, A T]]
+[[Category: Baker AT]]
-[[Category: Mohammed, F]]
+[[Category: Mohammed F]]
-[[Category: Salim, M]]
+[[Category: Salim M]]
-[[Category: Willcox, B E]]
+[[Category: Willcox BE]]
-[[Category: B30 2]]
-[[Category: Butyrophilin]]
-[[Category: Signaling protein]]

5lyg

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF INTRACELLULAR B30.2 DOMAIN OF BTN3A1 BOUND TO MALONATE

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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