OCA at 11:35, 26 August 2020

2020-08-26T11:35:43Z

←Older revision		Revision as of 11:35, 26 August 2020
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	==CryoEM Structure of GABAB1b Homodimer==		==CryoEM Structure of GABAB1b Homodimer==
-	<StructureSection load='6w2y' size='340' side='right'caption='[[6w2y]]' scene=''>	+	<StructureSection load='6w2y' size='340' side='right'caption='[[6w2y]], [[Resolution\|resolution]] 3.20Å' 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=6W2Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W2Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w2y]] is a 2 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=6W2Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W2Y 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=6w2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w2y OCA], [http://pdbe.org/6w2y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w2y RCSB], [http://www.ebi.ac.uk/pdbsum/6w2y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w2y 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=L9Q:(1S)-2-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(OCTADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>L9Q</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SGG:[(2~{S})-3-[[(1~{S})-1-(3,4-dichlorophenyl)ethyl]amino]-2-oxidanyl-propyl]-(phenylmethyl)phosphinic+acid'>SGG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GABBR1, GPRC3A ([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://proteopedia.org/fgij/fg.htm?mol=6w2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w2y OCA], [http://pdbe.org/6w2y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w2y RCSB], [http://www.ebi.ac.uk/pdbsum/6w2y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w2y ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GABR1_HUMAN GABR1_HUMAN]] Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.<ref>PMID:9844003</ref> <ref>PMID:9872316</ref> <ref>PMID:18165688</ref> <ref>PMID:22660477</ref> Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.<ref>PMID:9844003</ref> <ref>PMID:9872316</ref> <ref>PMID:18165688</ref> <ref>PMID:22660477</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	GABA (gamma-aminobutyric acid) stimulation of the metabotropic GABAB receptor results in prolonged inhibition of neurotransmission that is central to brain physiology(1). GABAB belongs to the Family C of G protein-coupled receptors (GPCRs), which operate as dimers to relay synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins(2,3). GABAB, however, is unique in its function as an obligate heterodimer in which agonist binding and G protein activation take place on distinct subunits(4,5). Here we show structures of heterodimeric and homodimeric full-length GABAB receptors. Complemented by cellular signaling assays and atomistic simulations, the structures reveal an essential role for the GABAB extracellular loop 2 (ECL2) in relaying structural transitions by ordering the linker connecting the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of both GABAB subunits caps and interacts with the hydrophilic head of a phospholipid occupying the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G protein. These results provide a starting framework to decipher mechanistic modes of signal transduction mediated by GABAB dimers and have important implications for rational drug design targeting these receptors.
		+
		+	Structures of metabotropic GABAB receptor.,Papasergi-Scott MM, Robertson MJ, Seven AB, Panova O, Mathiesen JM, Skiniotis G Nature. 2020 Jun 24. pii: 10.1038/s41586-020-2469-4. doi:, 10.1038/s41586-020-2469-4. PMID:32580208<ref>PMID:32580208</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6w2y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[GABA receptor 3D structures\|GABA receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Papasergi-Scott MM]]	+	[[Category: Papasergi-Scott, M M]]
-	[[Category: Robertson MJ]]	+	[[Category: Robertson, M J]]
-	[[Category: Skiniotis G]]	+	[[Category: Skiniotis, G]]
		+	[[Category: Gpcr]]
		+	[[Category: Homodimer]]
		+	[[Category: Inhibitor]]
		+	[[Category: Signaling protein]]

OCA at 14:39, 8 July 2020

2020-07-08T14:39:26Z

←Older revision		Revision as of 14:39, 8 July 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6w2y is ~~ON HOLD~~	+	==CryoEM Structure of GABAB1b Homodimer==
-		+	<StructureSection load='6w2y' size='340' side='right'caption='[[6w2y]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W2Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W2Y 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=6w2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w2y OCA], [http://pdbe.org/6w2y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w2y RCSB], [http://www.ebi.ac.uk/pdbsum/6w2y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w2y ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Papasergi-Scott MM]]
		+	[[Category: Robertson MJ]]
		+	[[Category: Skiniotis G]]

OCA at 08:31, 17 June 2020

2020-06-17T08:31:35Z

←Older revision		Revision as of 08:31, 17 June 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6w2y is ON HOLD ~~until Paper Publication~~	+	The entry 6w2y is ON HOLD

	Authors:		Authors:

OCA at 04:12, 22 April 2020

2020-04-22T04:12:22Z

←Older revision		Revision as of 04:12, 22 April 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6w2y is ON HOLD	+	The entry 6w2y is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6w2y" [edit=sysop:move=sysop]

2020-03-18T08:31:10Z

Protected "6w2y" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:31, 18 March 2020

OCA: New page: '''Unreleased structure''' The entry 6w2y is ON HOLD Authors: Description: Category: Unreleased Structures

2020-03-18T08:31:09Z

New page: '''Unreleased structure''' The entry 6w2y is ON HOLD Authors: Description: Category: Unreleased Structures

New page