8ize - Revision history

OCA at 11:19, 14 March 2024

2024-03-14T11:19:07Z

← Older revision		Revision as of 11:19, 14 March 2024
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	== Function ==		== Function ==
	[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>		[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 ==~~
	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 8ize" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:17, 20 September 2023

2023-09-20T18:17:10Z

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

	~~The entry~~ 8ize is ~~ON HOLD until Paper~~ Publication		==Crystal structure of intracellular B30.2 domain of BTN3A1 in complex with 4-HMBPP==
			<StructureSection load='8ize' size='340' side='right'caption='[[8ize]], [[Resolution\|resolution]] 1.40Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8ize]] 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=8IZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IZE 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]] 1.4Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=S9R:[(E)-3-(hydroxymethyl)pent-2-enyl]+phosphono+hydrogen+phosphate'>S9R</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=8ize FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ize OCA], [https://pdbe.org/8ize PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ize RCSB], [https://www.ebi.ac.uk/pdbsum/8ize PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ize ProSAT]</span></td></tr>
			</table>
			== Function ==
			[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 ==
			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:~~ Yang, Y~~.Y.~~, Yi, S~~.M.~~, ~~Huang~~, J.W., Chen, ~~C.C.~~, Guo, R.T.		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 in complex with 4~~-~~HMBPP~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: ~~Huang, J.W~~]]		<div class="pdbe-citations 8ize" style="background-color:#fffaf0;"></div>
	[[Category: ~~Yi, S.M~~]]		== References ==
	[[Category: ~~Chen, C.C~~]]		<references/>
	[[Category: ~~Guo, R.T~~]]		__TOC__
	[[Category: ~~Yang, Y.Y~~]]		</StructureSection>
			[[Category: Homo sapiens]]
			[[Category: Large Structures]]
			[[Category: Chen CC]]
			[[Category: Guo RT]]
			[[Category: Huang JW]]
			[[Category: Yang YY]]
			[[Category: Yi SM]]

OCA at 07:57, 19 April 2023

2023-04-19T07:57:16Z

← Older revision		Revision as of 07:57, 19 April 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8ize is ON HOLD		The entry 8ize is ON HOLD until Paper Publication

	Authors: Yang, Y.Y., Yi, S.M., Huang, J.W., Chen, C.C., Guo, R.T.		Authors: Yang, Y.Y., Yi, S.M., Huang, J.W., Chen, C.C., Guo, R.T.
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	Description: Crystal structure of intracellular B30.2 domain of BTN3A1 in complex with 4-HMBPP		Description: Crystal structure of intracellular B30.2 domain of BTN3A1 in complex with 4-HMBPP
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	~~[[Category: Chen, C.C]]~~
	[[Category: Huang, J.W]]		[[Category: Huang, J.W]]
	[[Category: Yi, S.M]]		[[Category: Yi, S.M]]
			[[Category: Chen, C.C]]
	[[Category: Guo, R.T]]		[[Category: Guo, R.T]]
	[[Category: Yang, Y.Y]]		[[Category: Yang, Y.Y]]

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

2023-04-12T18:51:46Z

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

← Older revision	Revision as of 18:51, 12 April 2023
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8ize is ON HOLD Authors: Yang, Y.Y., Yi, S.M., Huang, J.W., Chen, C.C., Guo, R.T. Description: Crystal structure of intracellular B30.2 domain of B...

2023-04-12T18:51:45Z

New page: '''Unreleased structure''' The entry 8ize is ON HOLD Authors: Yang, Y.Y., Yi, S.M., Huang, J.W., Chen, C.C., Guo, R.T. Description: Crystal structure of intracellular B30.2 domain of B...

New page

'''Unreleased structure'''

The entry 8ize is ON HOLD

Authors: Yang, Y.Y., Yi, S.M., Huang, J.W., Chen, C.C., Guo, R.T.

Description: Crystal structure of intracellular B30.2 domain of BTN3A1 in complex with 4-HMBPP
[[Category: Unreleased Structures]]
[[Category: Chen, C.C]]
[[Category: Huang, J.W]]
[[Category: Yi, S.M]]
[[Category: Guo, R.T]]
[[Category: Yang, Y.Y]]