6d1s - Revision history

OCA at 14:32, 13 March 2024

OCA — Wed, 13 Mar 2024 14:32:04 GMT

←Older revision		Revision as of 14:32, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6d1s' size='340' side='right'caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='6d1s' size='340' side='right'caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d1s]] is a 10 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=6D1S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6D1S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d1s]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Dickeya_dadantii_3937 Dickeya dadantii 3937] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D1S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D1S FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~GABRA1 (~~[~~http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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]] 3.2Å</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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [~~http~~://pdbe.org/6d1s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s 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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [https://pdbe.org/6d1s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [https://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color~~:~~#fffaf0~~;">	+	== Disease ==
-	== ~~Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/GBRA1_HUMAN GBRA1_HUMAN] Juvenile myoclonic epilepsy;Childhood absence epilepsy;Dravet syndrome. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
-	~~Type A gamma-aminobutyric acid receptors (GABAARs) are~~ inhibitory ~~pentameric ligand-gated ion channels~~ in the brain. ~~Many anesthetics~~ and ~~neurosteroids act through binding~~ to ~~the GABAAR transmembrane domain (TMD), but the structural basis of their actions is not well understood~~ and ~~no resting-state GABAAR structure has been determined. Here~~, ~~we report crystal structures of apo and the neurosteroid anesthetic alphaxalone-~~bound desensitized chimeric alpha1GABAAR (ELIC-alpha1GABAAR). The chimera retains the functional and pharmacological properties of GABAARs, including potentiation, activation and desensitization by alphaxalone. The apo-state structure reveals an unconventional activation gate at ~~the intracellular end of the pore. The desensitized structure illustrates molecular determinants for alphaxalone~~ binding ~~to an inter-subunit TMD~~ site. ~~These structures suggest a plausible signaling pathway from alphaxalone binding at the bottom of the TMD to the~~ channel ~~gate in the pore-lining TM2 through the TM1-TM2 linker. The study provides a framework to discover new GABAAR modulators with therapeutic potential~~.	+	== Function ==
		+	[https://www.uniprot.org/uniprot/E0SJQ4_DICD3 E0SJQ4_DICD3] [https://www.uniprot.org/uniprot/GBRA1_HUMAN GBRA1_HUMAN] Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).

-	Structural basis of neurosteroid anesthetic action on GABAA receptors.,Chen Q, Wells MM, Arjunan P, Tillman TS, Cohen AE, Xu Y, Tang P Nat Commun. 2018 Sep 28;9(1):3972. doi: 10.1038/s41467-018-06361-4. PMID:30266951<ref>PMID:30266951</ref>	+	==See Also==
-		+	*[[GABA receptor 3D structures\|GABA receptor 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6d1s" style="background-color:#fffaf0;"></div>~~	+
-	== ~~References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Dickeya dadantii 3937]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arjunan, P]]	+	[[Category: Arjunan P]]
-	[[Category: Chen, Q]]	+	[[Category: Chen Q]]
-	[[Category: Cohen~~, A E~~]]	+	[[Category: Cohen AE]]
-	[[Category: Tang, P]]	+	[[Category: Tang P]]
-	[[Category: Xu, Y]]	+	[[Category: Xu Y]]
-	~~[[Category: Alphaxalone]]~~	+
-	~~[[Category: Anesthetic]]~~	+
-	~~[[Category: Gabaa receptor]]~~	+
-	~~[[Category: Neurosteroid]]~~	+
-	~~[[Category: Protein transport~~]]	+

OCA at 09:56, 18 December 2019

OCA — Wed, 18 Dec 2019 09:56:22 GMT

←Older revision		Revision as of 09:56, 18 December 2019
Line 1:		Line 1:

	==Crystal structure of an apo chimeric human alpha1GABAA receptor==		==Crystal structure of an apo chimeric human alpha1GABAA receptor==
-	<StructureSection load='6d1s' size='340' side='right' caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>	+	<StructureSection load='6d1s' size='340' side='right'caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6d1s]] is a 10 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=6D1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D1S FirstGlance]. <br>		<table><tr><td colspan='2'>[[6d1s]] is a 10 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=6D1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D1S FirstGlance]. <br>
Line 21:		Line 21:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Arjunan, P]]		[[Category: Arjunan, P]]
	[[Category: Chen, Q]]		[[Category: Chen, Q]]

OCA at 06:47, 24 October 2018

OCA — Wed, 24 Oct 2018 06:47:36 GMT

←Older revision		Revision as of 06:47, 24 October 2018
Line 9:		Line 9:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	A ~~unique aspect of arrestin~~-~~3 is its ability to support both receptor~~-~~dependent~~ and ~~receptor~~-~~independent signaling~~. Here, we ~~show that inositol hexakisphosphate (IP6) is a non-receptor activator~~ of ~~arrestin-3~~ and ~~report~~ the ~~structure of IP6~~-~~activated arrestin~~-~~3 at 2~~.~~4-A resolution. IP6-activated arrestin-3 exhibits an inter-domain twist~~ and ~~a displaced C-tail~~, ~~hallmarks of active arrestin. IP6 binds to the arrestin phosphate sensor~~, and ~~is stabilized~~ by ~~trimerization~~. ~~Analysis of the trimerization surface, which is also the receptor~~-~~binding surface, suggests a feature called~~ the ~~finger loop as a key region~~ of the ~~activation sensor~~. ~~We show that finger loop helicity and flexibility may underlie coupling~~ to ~~hundreds of diverse receptors and also promote arrestin~~-~~3 activation by IP6~~. ~~Importantly, we show that effector-~~binding ~~sites on arrestins have distinct conformations~~ in the ~~basal and activated states, acting as switch regions. These switch regions may work with~~ the ~~inter~~-~~domain twist~~ to ~~initiate and direct arrestin-mediated signaling~~.	+	Type A gamma-aminobutyric acid receptors (GABAARs) are inhibitory pentameric ligand-gated ion channels in the brain. Many anesthetics and neurosteroids act through binding to the GABAAR transmembrane domain (TMD), but the structural basis of their actions is not well understood and no resting-state GABAAR structure has been determined. Here, we report crystal structures of apo and the neurosteroid anesthetic alphaxalone-bound desensitized chimeric alpha1GABAAR (ELIC-alpha1GABAAR). The chimera retains the functional and pharmacological properties of GABAARs, including potentiation, activation and desensitization by alphaxalone. The apo-state structure reveals an unconventional activation gate at the intracellular end of the pore. The desensitized structure illustrates molecular determinants for alphaxalone binding to an inter-subunit TMD site. These structures suggest a plausible signaling pathway from alphaxalone binding at the bottom of the TMD to the channel gate in the pore-lining TM2 through the TM1-TM2 linker. The study provides a framework to discover new GABAAR modulators with therapeutic potential.

-	Structural basis of ~~arrestin-3 activation and signaling~~.,Chen Q, ~~Perry NA~~, ~~Vishnivetskiy SA~~, ~~Berndt S~~, ~~Gilbert NC~~, ~~Zhuo~~ Y, ~~Singh PK, Tholen J, Ohi MD, Gurevich EV, Brautigam CA, Klug CS, Gurevich VV, Iverson TM~~ Nat Commun. ~~2017 Nov 10~~;8(1):~~1427~~. doi: 10.1038/s41467-~~017~~-~~01218~~-8. PMID:~~29127291~~<ref>PMID:~~29127291~~</ref>	+	Structural basis of neurosteroid anesthetic action on GABAA receptors.,Chen Q, Wells MM, Arjunan P, Tillman TS, Cohen AE, Xu Y, Tang P Nat Commun. 2018 Sep 28;9(1):3972. doi: 10.1038/s41467-018-06361-4. PMID:30266951<ref>PMID:30266951</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

OCA at 08:31, 10 October 2018

OCA — Wed, 10 Oct 2018 08:31:52 GMT

←Older revision		Revision as of 08:31, 10 October 2018
Line 7:		Line 7:
	<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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [http://pdbe.org/6d1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [http://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s ProSAT]</span></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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [http://pdbe.org/6d1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [http://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP6) is a non-receptor activator of arrestin-3 and report the structure of IP6-activated arrestin-3 at 2.4-A resolution. IP6-activated arrestin-3 exhibits an inter-domain twist and a displaced C-tail, hallmarks of active arrestin. IP6 binds to the arrestin phosphate sensor, and is stabilized by trimerization. Analysis of the trimerization surface, which is also the receptor-binding surface, suggests a feature called the finger loop as a key region of the activation sensor. We show that finger loop helicity and flexibility may underlie coupling to hundreds of diverse receptors and also promote arrestin-3 activation by IP6. Importantly, we show that effector-binding sites on arrestins have distinct conformations in the basal and activated states, acting as switch regions. These switch regions may work with the inter-domain twist to initiate and direct arrestin-mediated signaling.
		+
		+	Structural basis of arrestin-3 activation and signaling.,Chen Q, Perry NA, Vishnivetskiy SA, Berndt S, Gilbert NC, Zhuo Y, Singh PK, Tholen J, Ohi MD, Gurevich EV, Brautigam CA, Klug CS, Gurevich VV, Iverson TM Nat Commun. 2017 Nov 10;8(1):1427. doi: 10.1038/s41467-017-01218-8. PMID:29127291<ref>PMID:29127291</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6d1s" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:45, 3 October 2018

OCA — Wed, 03 Oct 2018 08:45:58 GMT

←Older revision		Revision as of 08:45, 3 October 2018
Line 3:		Line 3:
	<StructureSection load='6d1s' size='340' side='right' caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='6d1s' size='340' side='right' caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d1s]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D1S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d1s]] is a 10 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=6D1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D1S FirstGlance]. <br>
-	</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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [http://pdbe.org/6d1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [http://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GABRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [http://pdbe.org/6d1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [http://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Arjunan, P]]		[[Category: Arjunan, P]]
	[[Category: Chen, Q]]		[[Category: Chen, Q]]

OCA at 06:07, 22 August 2018

OCA — Wed, 22 Aug 2018 06:07:59 GMT

←Older revision		Revision as of 06:07, 22 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6d1s is ON HOLD until Paper Publication~~	+	==Crystal structure of an apo chimeric human alpha1GABAA receptor==
-		+	<StructureSection load='6d1s' size='340' side='right' caption='[[6d1s]], [[Resolution\|resolution]] 3.20Å' scene=''>
-	~~Authors: Chen, Q., Arjunan, P., Cohen, A.E., Xu, Y., Tang, P.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6d1s]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D1S FirstGlance]. <br>
-	~~Description:~~ Crystal structure of an apo chimeric human alpha1GABAA receptor	+	</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=6d1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1s OCA], [http://pdbe.org/6d1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d1s RCSB], [http://www.ebi.ac.uk/pdbsum/6d1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1s ProSAT]</span></td></tr>
-	[[~~Category: Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Cohen, A~~.E]]	+	__TOC__
-	[[~~Category~~: ~~Tang~~, P]]	+	</StructureSection>
	[[Category: Arjunan, P]]		[[Category: Arjunan, P]]
	[[Category: Chen, Q]]		[[Category: Chen, Q]]
		+	[[Category: Cohen, A E]]
		+	[[Category: Tang, P]]
	[[Category: Xu, Y]]		[[Category: Xu, Y]]
		+	[[Category: Alphaxalone]]
		+	[[Category: Anesthetic]]
		+	[[Category: Gabaa receptor]]
		+	[[Category: Neurosteroid]]
		+	[[Category: Protein transport]]

OCA at 04:05, 25 April 2018

OCA — Wed, 25 Apr 2018 04:05:04 GMT

←Older revision		Revision as of 04:05, 25 April 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6d1s is ON HOLD	+	The entry 6d1s is ON HOLD until Paper Publication

	Authors: Chen, Q., Arjunan, P., Cohen, A.E., Xu, Y., Tang, P.		Authors: Chen, Q., Arjunan, P., Cohen, A.E., Xu, Y., Tang, P.
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	[[Category: Cohen, A.E]]		[[Category: Cohen, A.E]]
	[[Category: Tang, P]]		[[Category: Tang, P]]
-	[[Category: Xu, Y]]
	[[Category: Arjunan, P]]		[[Category: Arjunan, P]]
	[[Category: Chen, Q]]		[[Category: Chen, Q]]
		+	[[Category: Xu, Y]]

OCA: Protected "6d1s" [edit=sysop:move=sysop]

OCA — Wed, 18 Apr 2018 04:21:53 GMT

Protected "6d1s" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:21, 18 April 2018

OCA: New page: '''Unreleased structure''' The entry 6d1s is ON HOLD Authors: Chen, Q., Arjunan, P., Cohen, A.E., Xu, Y., Tang, P. Description: Crystal structure of an apo chimeric human alpha1GABAA r...

OCA — Wed, 18 Apr 2018 04:21:52 GMT

New page: '''Unreleased structure''' The entry 6d1s is ON HOLD Authors: Chen, Q., Arjunan, P., Cohen, A.E., Xu, Y., Tang, P. Description: Crystal structure of an apo chimeric human alpha1GABAA r...

New page

'''Unreleased structure'''

The entry 6d1s is ON HOLD

Authors: Chen, Q., Arjunan, P., Cohen, A.E., Xu, Y., Tang, P.

Description: Crystal structure of an apo chimeric human alpha1GABAA receptor
[[Category: Unreleased Structures]]
[[Category: Cohen, A.E]]
[[Category: Tang, P]]
[[Category: Xu, Y]]
[[Category: Arjunan, P]]
[[Category: Chen, Q]]