OCA at 13:09, 4 May 2022

OCA — Wed, 04 May 2022 13:09:21 GMT

←Older revision		Revision as of 13:09, 4 May 2022
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	==Complex GNGN2 of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM)==		==Complex GNGN2 of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM)==
-	<StructureSection load='7tnm' size='340' side='right'caption='[[7tnm]]' scene=''>	+	<StructureSection load='7tnm' size='340' side='right'caption='[[7tnm]], [[Resolution\|resolution]] 4.74Å' 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=7TNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TNM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7tnm]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TNM 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=7tnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tnm OCA], [https://pdbe.org/7tnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tnm RCSB], [https://www.ebi.ac.uk/pdbsum/7tnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tnm 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=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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=7tnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tnm OCA], [https://pdbe.org/7tnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tnm RCSB], [https://www.ebi.ac.uk/pdbsum/7tnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tnm ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate(1-3). An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1-O4)(4-6). Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs)(6-10). Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit gamma2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity.
		+
		+	Opening of glutamate receptor channel to subconductance levels.,Yelshanskaya MV, Patel DS, Kottke CM, Kurnikova MG, Sobolevsky AI Nature. 2022 Apr 20. pii: 10.1038/s41586-022-04637-w. doi:, 10.1038/s41586-022-04637-w. PMID:35444281<ref>PMID:35444281</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7tnm" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sobolevsky AI]]	+	[[Category: Sobolevsky, A I]]
-	[[Category: Yelshanskaya MV]]	+	[[Category: Yelshanskaya, M V]]
		+	[[Category: Agonist]]
		+	[[Category: Ampa]]
		+	[[Category: Complex]]
		+	[[Category: Cryo-em]]
		+	[[Category: Gating]]
		+	[[Category: Glutamate]]
		+	[[Category: Iglur]]
		+	[[Category: Membrane protein]]
		+	[[Category: Opening]]
		+	[[Category: Positive allosteric modulator]]
		+	[[Category: Stargazin]]
		+	[[Category: Subconductance level]]

OCA at 02:57, 21 April 2022

OCA — Thu, 21 Apr 2022 02:57:29 GMT

←Older revision		Revision as of 02:57, 21 April 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7tnm ~~is ON HOLD until Paper Publication~~	+	==Complex GNGN2 of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM)==
-		+	<StructureSection load='7tnm' size='340' side='right'caption='[[7tnm]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TNM 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=7tnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tnm OCA], [https://pdbe.org/7tnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tnm RCSB], [https://www.ebi.ac.uk/pdbsum/7tnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tnm ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Sobolevsky AI]]
		+	[[Category: Yelshanskaya MV]]

OCA at 05:03, 2 March 2022

OCA — Wed, 02 Mar 2022 05:03:24 GMT

←Older revision		Revision as of 05:03, 2 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 02 Feb 2022 05:37:24 GMT

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

←Older revision

Revision as of 05:37, 2 February 2022

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

OCA — Wed, 02 Feb 2022 05:37:22 GMT

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

New page

'''Unreleased structure'''

The entry 7tnm is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7tnm - Revision history

OCA at 13:09, 4 May 2022

OCA at 02:57, 21 April 2022

OCA at 05:03, 2 March 2022

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

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