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5zxk

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Current revision

Crystal structure of intracellular B30.2 domain of BTN3A1 in complex with HMBPP

Structural highlights

5zxk 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 1.96Å
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 and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vgamma9Vdelta2 T cell receptor (TCR). Here, we examined the molecular basis of this "inside-out" triggering mechanism. Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for gammadelta T cell activation. Analyses with chemical probes and molecular dynamic simulations demonstrated that dimerized intracellular proteins cooperate in sensing HMBPP to enhance the efficiency of gammadelta T cell activation. HMBPP binding to butyrophilin doubled the binding force between a gammadelta T cell and a target cell during "outside" signaling, as measured by single-cell force microscopy. Our findings provide insight into the "inside-out" triggering of Vgamma9Vdelta2 T cell activation by phosphoantigen-bound butyrophilin, facilitating immunotherapeutic drug design.

A Structural Change in Butyrophilin upon Phosphoantigen Binding Underlies Phosphoantigen-Mediated Vgamma9Vdelta2 T Cell Activation.,Yang Y, Li L, Yuan L, Zhou X, Duan J, Xiao H, Cai N, Han S, Ma X, Liu W, Chen CC, Wang L, Li X, Chen J, Kang N, Chen J, Shen Z, Malwal SR, Liu W, Shi Y, Oldfield E, Guo RT, Zhang Y Immunity. 2019 Mar 14. pii: S1074-7613(19)30083-4. doi:, 10.1016/j.immuni.2019.02.016. PMID:30902636^[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
↑ Yang Y, Li L, Yuan L, Zhou X, Duan J, Xiao H, Cai N, Han S, Ma X, Liu W, Chen CC, Wang L, Li X, Chen J, Kang N, Chen J, Shen Z, Malwal SR, Liu W, Shi Y, Oldfield E, Guo RT, Zhang Y. A Structural Change in Butyrophilin upon Phosphoantigen Binding Underlies Phosphoantigen-Mediated Vgamma9Vdelta2 T Cell Activation. Immunity. 2019 Mar 14. pii: S1074-7613(19)30083-4. doi:, 10.1016/j.immuni.2019.02.016. PMID:30902636 doi:http://dx.doi.org/10.1016/j.immuni.2019.02.016

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/5zxk"

@@ Line 3: / Line 3: @@
 <StructureSection load='5zxk' size='340' side='right'caption='[[5zxk]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5zxk]] 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=5ZXK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZXK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5zxk]] 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=5ZXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZXK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H6P:(2E)-4-HYDROXY-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>H6P</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]] 1.96&#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=H6P:(2E)-4-HYDROXY-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>H6P</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=5zxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zxk OCA], [http://pdbe.org/5zxk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zxk RCSB], [http://www.ebi.ac.uk/pdbsum/5zxk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zxk 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=5zxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zxk OCA], [https://pdbe.org/5zxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zxk RCSB], [https://www.ebi.ac.uk/pdbsum/5zxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zxk 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: Chen, C C]]
+[[Category: Chen CC]]
-[[Category: Guo, R T]]
+[[Category: Guo RT]]
-[[Category: Liu, W D]]
+[[Category: Liu WD]]
-[[Category: Yang, Y Y]]
+[[Category: Yang YY]]
-[[Category: Zhang, Y H]]
+[[Category: Zhang YH]]
-[[Category: Agonist]]
-[[Category: Signaling protein]]
-[[Category: Substrate binding]]

5zxk

From Proteopedia

Current revision

Crystal structure of intracellular B30.2 domain of BTN3A1 in complex with HMBPP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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