OCA at 04:07, 8 September 2022

OCA — Thu, 08 Sep 2022 04:07:19 GMT

←Older revision		Revision as of 04:07, 8 September 2022
Line 1:		Line 1:

-	====	+	==Cryo-EM structure of a membrane protein(CS)==
-	<StructureSection load='7fjf' size='340' side='right'caption='[[7fjf]]' scene=''>	+	<StructureSection load='7fjf' size='340' side='right'caption='[[7fjf]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7fjf]] is a 8 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=7FJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FJF FirstGlance]. <br>
-	</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=7fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fjf OCA], [https://pdbe.org/7fjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fjf RCSB], [https://www.ebi.ac.uk/pdbsum/7fjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fjf ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C3S:CHOLEST-5-EN-3-YL+HYDROGEN+SULFATE'>C3S</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=7fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fjf OCA], [https://pdbe.org/7fjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fjf RCSB], [https://www.ebi.ac.uk/pdbsum/7fjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fjf ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/A0A0G2JMB4_HUMAN A0A0G2JMB4_HUMAN]] [[https://www.uniprot.org/uniprot/TVB65_HUMAN TVB65_HUMAN]] V region of the variable domain of T cell receptor (TR) beta chain that participates in the antigen recognition (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585).<ref>PMID:26875526</ref> <ref>PMID:15040585</ref> <ref>PMID:23524462</ref> <ref>PMID:24600447</ref> <ref>PMID:25493333</ref> [[https://www.uniprot.org/uniprot/TRBR1_HUMAN TRBR1_HUMAN]] The beta chain of TRAV2701J4201C01/TRBV1901J2S701C02 alpha-beta T cell receptor (TR) clonotype that is specific for HLA-A02:01-restricted M/matrix protein 1 immunodominant epitope GILGFVFTL of influenza A virus (IAV). Classified as a public TCR clonotype, it is preferentially selected in effector memory CD8-positive T cells among multiple HLA-A02:01 carriers/individuals and confers long-lived immunity against IAV infection. Can cross-recognize sporadically emerging IAV variants by molecular mimicry, inducing immunity toward different influenza strains (PubMed:1833769, PubMed:7807026, PubMed:29997621, PubMed:27036003, PubMed:12796775, PubMed:18275829). Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).[UniProtKB:A0A075B6N1]<ref>PMID:12796775</ref> <ref>PMID:18275829</ref> <ref>PMID:1833769</ref> <ref>PMID:27036003</ref> <ref>PMID:29997621</ref> <ref>PMID:7807026</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cholesterol molecules specifically bind to the resting alphabetaTCR to inhibit cytoplasmic CD3zeta ITAM phosphorylation through sequestering the TCR-CD3 complex in an inactive conformation. The mechanisms of cholesterol-mediated inhibition of TCR-CD3 and its activation remain unclear. Here, we present cryoelectron microscopy structures of cholesterol- and cholesterol sulfate (CS)-inhibited TCR-CD3 complexes and an auto-active TCR-CD3 variant. The structures reveal that cholesterol molecules act like a latch to lock CD3zeta into an inactive conformation in the membrane. Mutations impairing binding of cholesterol molecules to the tunnel result in the movement of the proximal C terminus of the CD3zeta transmembrane helix, thereby activating the TCR-CD3 complex in human cells. Together, our data reveal the structural basis of TCR inhibition by cholesterol, illustrate how the cholesterol-binding tunnel is allosterically coupled to TCR triggering, and lay a foundation for the development of immunotherapies through directly targeting the TCR-CD3 complex.
		+
		+	Cholesterol inhibits TCR signaling by directly restricting TCR-CD3 core tunnel motility.,Chen Y, Zhu Y, Li X, Gao W, Zhen Z, Dong, Huang B, Ma Z, Zhang A, Song X, Ma Y, Guo C, Zhang F, Huang Z Mol Cell. 2022 Apr 7;82(7):1278-1287.e5. doi: 10.1016/j.molcel.2022.02.017. Epub , 2022 Mar 9. PMID:35271814<ref>PMID:35271814</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7fjf" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z~~-disk~~]]	+	[[Category: Chen Y]]
		+	[[Category: Gao W]]
		+	[[Category: Guo C]]
		+	[[Category: Huang Z]]
		+	[[Category: Zhang A]]
		+	[[Category: Zhu Y]]

OCA at 18:00, 27 July 2022

OCA — Wed, 27 Jul 2022 18:00:18 GMT

←Older revision		Revision as of 18:00, 27 July 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7fjf ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7fjf' size='340' side='right'caption='[[7fjf]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fjf OCA], [https://pdbe.org/7fjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fjf RCSB], [https://www.ebi.ac.uk/pdbsum/7fjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fjf ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 11:45, 29 December 2021

OCA — Wed, 29 Dec 2021 11:45:20 GMT

←Older revision		Revision as of 11:45, 29 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7fjf is ON HOLD	+	The entry 7fjf is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7fjf" [edit=sysop:move=sysop]

OCA — Wed, 11 Aug 2021 04:59:32 GMT

Protected "7fjf" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:59, 11 August 2021

OCA: New page: '''Unreleased structure''' The entry 7fjf is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 11 Aug 2021 04:59:31 GMT

New page: '''Unreleased structure''' The entry 7fjf is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7fjf is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7fjf - Revision history

OCA at 04:07, 8 September 2022

OCA at 18:00, 27 July 2022

OCA at 11:45, 29 December 2021

OCA: Protected "7fjf" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7fjf is ON HOLD Authors: Description: Category: Unreleased Structures