8jye - Revision history

OCA at 11:19, 14 March 2024

OCA — Thu, 14 Mar 2024 11:19:45 GMT

←Older revision		Revision as of 11:19, 14 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/BT2A1_HUMAN BT2A1_HUMAN]		[https://www.uniprot.org/uniprot/BT2A1_HUMAN BT2A1_HUMAN]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	In both cancer and infections, diseased cells are presented to human Vgamma9Vdelta2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A1(1-4). Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vgamma9Vdelta2 T cell activation. Analyses using structure-based molecular-dynamics simulations, (19)F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated gammadelta T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human gammadelta T cell function.
-
-	Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vgamma9Vdelta2 T cells.,Yuan L, Ma X, Yang Y, Qu Y, Li X, Zhu X, Ma W, Duan J, Xue J, Yang H, Huang JW, Yi S, Zhang M, Cai N, Zhang L, Ding Q, Lai K, Liu C, Zhang L, Liu X, Yao Y, Zhou S, Li X, Shen P, Chang Q, Malwal SR, He Y, Li W, Chen C, Chen CC, Oldfield E, Guo RT, Zhang Y Nature. 2023 Sep 6. doi: 10.1038/s41586-023-06525-3. PMID:37674084<ref>PMID:37674084</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8jye" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 18:17, 20 September 2023

OCA — Wed, 20 Sep 2023 18:17:25 GMT

←Older revision		Revision as of 18:17, 20 September 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8jye is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of Intracellular B30.2 Domain of BTN3A1 and BTN2A1 in Complex with HMBPP==
		+	<StructureSection load='8jye' size='340' side='right'caption='[[8jye]], [[Resolution\|resolution]] 2.18Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8jye]] is a 4 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=8JYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JYE FirstGlance]. <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]] 2.18Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=H6P:(2E)-4-HYDROXY-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>H6P</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=8jye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jye OCA], [https://pdbe.org/8jye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jye RCSB], [https://www.ebi.ac.uk/pdbsum/8jye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jye ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/BT2A1_HUMAN BT2A1_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In both cancer and infections, diseased cells are presented to human Vgamma9Vdelta2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A1(1-4). Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vgamma9Vdelta2 T cell activation. Analyses using structure-based molecular-dynamics simulations, (19)F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated gammadelta T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human gammadelta T cell function.

-	~~Authors:~~ Yuan, L~~.J.~~, Yang, Y~~.Y.~~, Li, X., ~~Cai~~, N~~.N.~~, ~~Chen~~, C.-C., ~~Guo~~, ~~R.-T.~~, ~~Zhang~~, Y.H.	+	Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vgamma9Vdelta2 T cells.,Yuan L, Ma X, Yang Y, Qu Y, Li X, Zhu X, Ma W, Duan J, Xue J, Yang H, Huang JW, Yi S, Zhang M, Cai N, Zhang L, Ding Q, Lai K, Liu C, Zhang L, Liu X, Yao Y, Zhou S, Li X, Shen P, Chang Q, Malwal SR, He Y, Li W, Chen C, Chen CC, Oldfield E, Guo RT, Zhang Y Nature. 2023 Sep 6. doi: 10.1038/s41586-023-06525-3. PMID:37674084<ref>PMID:37674084</ref>

-	~~Description: Crystal Structure~~ of ~~Intracellular B30~~.~~2 Domain~~ of ~~BTN3A1 and BTN2A1 in Complex with HMBPP~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Chen, C.-C~~]]	+	<div class="pdbe-citations 8jye" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Li, X~~]]	+	== References ==
-	[[Category: ~~Zhang, Y.H~~]]	+	<references/>
-	[[Category: Guo, R.-T]]	+	__TOC__
-	[[Category: ~~Yuan, L.J~~]]	+	</StructureSection>
-	[[Category: ~~Cai, N.N~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Yang, Y.Y~~]]	+	[[Category: Large Structures]]
		+	[[Category: Cai NN]]
		+	[[Category: Chen C-C]]
		+	[[Category: Guo R-T]]
		+	[[Category: Li X]]
		+	[[Category: Yang YY]]
		+	[[Category: Yuan LJ]]
		+	[[Category: Zhang YH]]

OCA: Protected "8jye" [edit=sysop:move=sysop]

OCA — Wed, 12 Jul 2023 04:03:01 GMT

Protected "8jye" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:03, 12 July 2023

OCA: New page: '''Unreleased structure''' The entry 8jye is ON HOLD until Paper Publication Authors: Yuan, L.J., Yang, Y.Y., Li, X., Cai, N.N., Chen, C.-C., Guo, R.-T., Zhang, Y.H. Description: Cryst...

OCA — Wed, 12 Jul 2023 04:02:58 GMT

New page: '''Unreleased structure''' The entry 8jye is ON HOLD until Paper Publication Authors: Yuan, L.J., Yang, Y.Y., Li, X., Cai, N.N., Chen, C.-C., Guo, R.-T., Zhang, Y.H. Description: Cryst...

New page

'''Unreleased structure'''

The entry 8jye is ON HOLD until Paper Publication

Authors: Yuan, L.J., Yang, Y.Y., Li, X., Cai, N.N., Chen, C.-C., Guo, R.-T., Zhang, Y.H.

Description: Crystal Structure of Intracellular B30.2 Domain of BTN3A1 and BTN2A1 in Complex with HMBPP
[[Category: Unreleased Structures]]
[[Category: Chen, C.-C]]
[[Category: Li, X]]
[[Category: Zhang, Y.H]]
[[Category: Guo, R.-T]]
[[Category: Yuan, L.J]]
[[Category: Cai, N.N]]
[[Category: Yang, Y.Y]]