OCA at 11:07, 15 November 2023

OCA — Wed, 15 Nov 2023 11:07:39 GMT

←Older revision		Revision as of 11:07, 15 November 2023
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-	====	+	==Cryo-EM structure of human full-length beta3gamma2 GABA(A)R in complex with GABA and nanobody Nb25==
-	<StructureSection load='7qnb' size='340' side='right'caption='[[7qnb]]' scene=''>	+	<StructureSection load='7qnb' size='340' side='right'caption='[[7qnb]], [[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'>[[7qnb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QNB 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=7qnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qnb OCA], [https://pdbe.org/7qnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qnb RCSB], [https://www.ebi.ac.uk/pdbsum/7qnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qnb ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7qnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qnb OCA], [https://pdbe.org/7qnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qnb RCSB], [https://www.ebi.ac.uk/pdbsum/7qnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qnb ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/GBRG2_HUMAN GBRG2_HUMAN] Childhood absence epilepsy;Dravet syndrome;Generalized epilepsy with febrile seizures-plus. 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. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GBRG2_HUMAN GBRG2_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.<ref>PMID:2538761</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Type A gamma-aminobutyric acid receptors (GABA(A)Rs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits(1,2) and can be modulated by essential medicines including general anaesthetics and benzodiazepines(3). Human GABA(A)R subunits are encoded by 19 paralogous genes that can, in theory, give rise to 495,235 receptor types. However, the principles that govern the formation of pentamers, the permutational landscape of receptors that may emerge from a subunit set and the effect that this has on GABAergic signalling remain largely unknown. Here we use cryogenic electron microscopy to determine the structures of extrasynaptic GABA(A)Rs assembled from alpha4, beta3 and delta subunits, and their counterparts incorporating gamma2 instead of delta subunits. In each case, we identified two receptor subtypes with distinct stoichiometries and arrangements, all four differing from those previously observed for synaptic, alpha1-containing receptors(4-7). This, in turn, affects receptor responses to physiological and synthetic modulators by creating or eliminating ligand-binding sites at subunit interfaces. We provide structural and functional evidence that selected GABA(A)R arrangements can act as coincidence detectors, simultaneously responding to two neurotransmitters: GABA and histamine. Using assembly simulations and single-cell RNA sequencing data(8,9), we calculated the upper bounds for receptor diversity in recombinant systems and in vivo. We propose that differential assembly is a pervasive mechanism for regulating the physiology and pharmacology of GABA(A)Rs.
		+
		+	Differential assembly diversifies GABA(A) receptor structures and signalling.,Sente A, Desai R, Naydenova K, Malinauskas T, Jounaidi Y, Miehling J, Zhou X, Masiulis S, Hardwick SW, Chirgadze DY, Miller KW, Aricescu AR Nature. 2022 Apr;604(7904):190-194. doi: 10.1038/s41586-022-04517-3. Epub 2022 , Mar 30. PMID:35355020<ref>PMID:35355020</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7qnb" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Lama glama]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Aricescu AR]]
		+	[[Category: Chirgadze DY]]
		+	[[Category: Desai R]]
		+	[[Category: Hardwick SW]]
		+	[[Category: Jounaidi Y]]
		+	[[Category: Malinauskas T]]
		+	[[Category: Masiulis S]]
		+	[[Category: Miehling J]]
		+	[[Category: Miller KW]]
		+	[[Category: Naydenova K]]
		+	[[Category: Sente A]]
		+	[[Category: Zhou X]]

OCA at 09:47, 13 April 2022

OCA — Wed, 13 Apr 2022 09:47:25 GMT

←Older revision		Revision as of 09:47, 13 April 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7qnb ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7qnb' size='340' side='right'caption='[[7qnb]]' 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=7qnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qnb OCA], [https://pdbe.org/7qnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qnb RCSB], [https://www.ebi.ac.uk/pdbsum/7qnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qnb ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 04:56, 16 March 2022

OCA — Wed, 16 Mar 2022 04:56:36 GMT

←Older revision		Revision as of 04:56, 16 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7qnb is ON HOLD ~~until sometime in the future~~	+	The entry 7qnb is ON HOLD

	Authors:		Authors:

OCA at 08:30, 12 January 2022

OCA — Wed, 12 Jan 2022 08:30:10 GMT

←Older revision		Revision as of 08:30, 12 January 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7qnb is ON HOLD	+	The entry 7qnb is ON HOLD until sometime in the future

	Authors:		Authors:

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

OCA — Wed, 29 Dec 2021 11:56:06 GMT

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

←Older revision

Revision as of 11:56, 29 December 2021

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

OCA — Wed, 29 Dec 2021 11:56:04 GMT

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

New page