OCA at 12:54, 24 January 2024

OCA — Wed, 24 Jan 2024 12:54:44 GMT

←Older revision		Revision as of 12:54, 24 January 2024
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	==ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and allosteric ligand FM26==		==ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and allosteric ligand FM26==
-	<StructureSection load='6t4t' size='340' side='right'caption='[[6t4t]]' scene=''>	+	<StructureSection load='6t4t' size='340' side='right'caption='[[6t4t]], [[Resolution\|resolution]] 1.62Å' 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=6T4T OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6T4T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6t4t]] 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=6T4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T4T FirstGlance]. <br>
-	</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=6t4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t4t OCA], [~~http~~://pdbe.org/6t4t PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6t4t RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6t4t PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6t4t ProSAT]</span></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]] 1.62Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HCD:(3ALPHA,8ALPHA)-CHOLEST-5-ENE-3,20-DIOL'>HCD</scene>, <scene name='pdbligand=L3E:4-[(~{E})-[3-[2-chloranyl-6-(trifluoromethyl)phenyl]-5-(1~{H}-pyrrol-3-yl)-1,2-oxazol-4-yl]methylideneamino]benzoic+acid'>L3E</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=6t4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t4t OCA], [https://pdbe.org/6t4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t4t RCSB], [https://www.ebi.ac.uk/pdbsum/6t4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t4t ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cooperative ligand binding is an important phenomenon in biological systems where ligand binding influences the binding of another ligand at an alternative site of the protein via an intramolecular network of interactions. The underlying mechanisms behind cooperative binding remain poorly understood, primarily due to the lack of structural data of these ternary complexes. Using time-resolved fluorescence resonance energy transfer (TR-FRET) studies, we show that cooperative ligand binding occurs for RORgammat, a nuclear receptor associated with the pathogenesis of autoimmune diseases. To provide the crucial structural insights, we solved 12 crystal structures of RORgammat simultaneously bound to various orthosteric and allosteric ligands. The presence of the orthosteric ligand induces a clamping motion of the allosteric pocket via helices 4 to 5. Additional molecular dynamics simulations revealed the unusual mechanism behind this clamping motion, with Ala355 shifting between helix 4 and 5. The orthosteric RORgammat agonists regulate the conformation of Ala355, thereby stabilizing the conformation of the allosteric pocket and cooperatively enhancing the affinity of the allosteric inverse agonists.
		+
		+	Cooperativity between the orthosteric and allosteric ligand binding sites of RORgammat.,de Vries RMJM, Meijer FA, Doveston RG, Leijten-van de Gevel IA, Brunsveld L Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2021287118. doi: , 10.1073/pnas.2021287118. PMID:33536342<ref>PMID:33536342</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6t4t" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Brunsveld L]]		[[Category: Brunsveld L]]
	[[Category: Meijer FA]]		[[Category: Meijer FA]]
	[[Category: De Vries RMJM]]		[[Category: De Vries RMJM]]

OCA at 09:33, 18 November 2020

OCA — Wed, 18 Nov 2020 09:33:24 GMT

←Older revision		Revision as of 09:33, 18 November 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6t4t is ~~ON HOLD until Paper Publication~~	+	==ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and allosteric ligand FM26==
-		+	<StructureSection load='6t4t' size='340' side='right'caption='[[6t4t]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T4T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6T4T FirstGlance]. <br>
-	~~Description~~:	+	</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=6t4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t4t OCA], [http://pdbe.org/6t4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t4t RCSB], [http://www.ebi.ac.uk/pdbsum/6t4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t4t ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Brunsveld L]]
		+	[[Category: Meijer FA]]
		+	[[Category: De Vries RMJM]]

OCA at 09:18, 29 July 2020

OCA — Wed, 29 Jul 2020 09:18:14 GMT

←Older revision		Revision as of 09:18, 29 July 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6t4t is ON HOLD	+	The entry 6t4t is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6t4t" [edit=sysop:move=sysop]

OCA — Wed, 23 Oct 2019 05:01:41 GMT

Protected "6t4t" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:01, 23 October 2019

OCA: New page: '''Unreleased structure''' The entry 6t4t is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 23 Oct 2019 05:01:38 GMT

New page: '''Unreleased structure''' The entry 6t4t is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6t4t is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6t4t - Revision history

OCA at 12:54, 24 January 2024

OCA at 09:33, 18 November 2020

OCA at 09:18, 29 July 2020

OCA: Protected "6t4t" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6t4t is ON HOLD Authors: Description: Category: Unreleased Structures