6wyl - Revision history

OCA at 14:47, 6 March 2024

OCA — Wed, 06 Mar 2024 14:47:35 GMT

←Older revision		Revision as of 14:47, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='6wyl' size='340' side='right'caption='[[6wyl]], [[Resolution\|resolution]] 3.90Å' scene=''>		<StructureSection load='6wyl' size='340' side='right'caption='[[6wyl]], [[Resolution\|resolution]] 3.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6wyl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Pyrococcus_horikoshii~~ Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6wyl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii_OT3 Pyrococcus horikoshii OT3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYL FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>~~</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]] 3.9Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~PH1295 ([https~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=70601 Pyrococcus horikoshii])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</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=6wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyl OCA], [https://pdbe.org/6wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyl RCSB], [https://www.ebi.ac.uk/pdbsum/6wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyl 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=6wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyl OCA], [https://pdbe.org/6wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyl RCSB], [https://www.ebi.ac.uk/pdbsum/6wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/GLT_PYRHO GLT_PYRHO]] Sodium-dependent, high-affinity amino acid transporter that mediates aspartate uptake (PubMed:17435767, PubMed:19380583, PubMed:17230192, Ref.11). Has only very low glutamate transport activity (PubMed:19380583, PubMed:17230192). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions, resulting in electrogenic transport (PubMed:17435767, PubMed:19380583, Ref.11). Na(+) binding enhances the affinity for aspartate (PubMed:19380583, Ref.11). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:17435767). In contrast to mammalian homologs, transport does not depend on pH or K(+) ions (PubMed:19380583).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19]	+	[https://www.uniprot.org/uniprot/GLT_PYRHO GLT_PYRHO] Sodium-dependent, high-affinity amino acid transporter that mediates aspartate uptake (PubMed:17435767, PubMed:19380583, PubMed:17230192, Ref.11). Has only very low glutamate transport activity (PubMed:19380583, PubMed:17230192). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions, resulting in electrogenic transport (PubMed:17435767, PubMed:19380583, Ref.11). Na(+) binding enhances the affinity for aspartate (PubMed:19380583, Ref.11). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:17435767). In contrast to mammalian homologs, transport does not depend on pH or K(+) ions (PubMed:19380583).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity(1). The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism(2-5). Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport(6-8). However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family.	+

-	Glutamate transporters have a chloride channel with two hydrophobic gates.,Chen I, Pant S, Wu Q, Cater RJ, Sobti M, Vandenberg RJ, Stewart AG, Tajkhorshid E, Font J, Ryan RM Nature. 2021 Feb 17. pii: 10.1038/s41586-021-03240-9. doi:, 10.1038/s41586-021-03240-9. PMID:33597752<ref>PMID:33597752</ref>	+	==See Also==
-		+	*[[Symporter 3D structures\|Symporter 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 6wyl" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 18:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Pyrococcus horikoshii]]	+	[[Category: Pyrococcus horikoshii OT3]]
-	[[Category: Chen, I]]	+	[[Category: Chen I]]
-	[[Category: Font, J]]	+	[[Category: Font J]]
-	[[Category: Ryan~~, R M~~]]	+	[[Category: Ryan RM]]
-	[[Category: Sobti, M]]	+	[[Category: Sobti M]]
-	[[Category: Stewart~~, A G]]~~	+	[[Category: Stewart AG]]
-	~~[[Category: Glutamate transporter homolog gltph]]~~	+
-	~~[[Category: Transport protein~~]]	+

OCA at 14:57, 3 March 2021

OCA — Wed, 03 Mar 2021 14:57:30 GMT

←Older revision		Revision as of 14:57, 3 March 2021
Line 1:		Line 1:

	==Cryo-EM structure of GltPh L152C-G351C mutant in the intermediate outward-facing state.==		==Cryo-EM structure of GltPh L152C-G351C mutant in the intermediate outward-facing state.==
-	<StructureSection load='6wyl' size='340' side='right'caption='[[6wyl]]' scene=''>	+	<StructureSection load='6wyl' size='340' side='right'caption='[[6wyl]], [[Resolution\|resolution]] 3.90Å' 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=6WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6wyl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYL 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=6wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyl OCA], [https://pdbe.org/6wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyl RCSB], [https://www.ebi.ac.uk/pdbsum/6wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyl 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=ASP:ASPARTIC+ACID'>ASP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PH1295 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=70601 Pyrococcus horikoshii])</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=6wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyl OCA], [https://pdbe.org/6wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyl RCSB], [https://www.ebi.ac.uk/pdbsum/6wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyl ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/GLT_PYRHO GLT_PYRHO]] Sodium-dependent, high-affinity amino acid transporter that mediates aspartate uptake (PubMed:17435767, PubMed:19380583, PubMed:17230192, Ref.11). Has only very low glutamate transport activity (PubMed:19380583, PubMed:17230192). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions, resulting in electrogenic transport (PubMed:17435767, PubMed:19380583, Ref.11). Na(+) binding enhances the affinity for aspartate (PubMed:19380583, Ref.11). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:17435767). In contrast to mammalian homologs, transport does not depend on pH or K(+) ions (PubMed:19380583).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity(1). The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism(2-5). Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport(6-8). However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family.
		+
		+	Glutamate transporters have a chloride channel with two hydrophobic gates.,Chen I, Pant S, Wu Q, Cater RJ, Sobti M, Vandenberg RJ, Stewart AG, Tajkhorshid E, Font J, Ryan RM Nature. 2021 Feb 17. pii: 10.1038/s41586-021-03240-9. doi:, 10.1038/s41586-021-03240-9. PMID:33597752<ref>PMID:33597752</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6wyl" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen I]]	+	[[Category: Pyrococcus horikoshii]]
-	[[Category: Font J]]	+	[[Category: Chen, I]]
-	[[Category: Ryan RM]]	+	[[Category: Font, J]]
-	[[Category: Sobti M]]	+	[[Category: Ryan, R M]]
-	[[Category: Stewart AG]]	+	[[Category: Sobti, M]]
		+	[[Category: Stewart, A G]]
		+	[[Category: Glutamate transporter homolog gltph]]
		+	[[Category: Transport protein]]

OCA at 09:56, 17 February 2021

OCA — Wed, 17 Feb 2021 09:56:42 GMT

←Older revision		Revision as of 09:56, 17 February 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6wyl is ON HOLD until Paper Publication~~	+	==Cryo-EM structure of GltPh L152C-G351C mutant in the intermediate outward-facing state.==
-		+	<StructureSection load='6wyl' size='340' side='right'caption='[[6wyl]]' scene=''>
-	~~Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYL FirstGlance]. <br>
-	~~Description:~~ Cryo-EM structure of GltPh L152C-G351C mutant in the intermediate outward-facing state.	+	</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=6wyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wyl OCA], [https://pdbe.org/6wyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wyl RCSB], [https://www.ebi.ac.uk/pdbsum/6wyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wyl ProSAT]</span></td></tr>
-	[[~~Category: Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Font, J]~~]	+	__TOC__
-	[[~~Category~~: ~~Stewart~~, A.G]]	+	</StructureSection>
-	[[Category: ~~Sobti, M~~]]	+	[[Category: Large Structures]]
-	[[Category: Chen, I]]	+	[[Category: Chen I]]
-	[[Category: Ryan~~, R.~~M]]	+	[[Category: Font J]]
		+	[[Category: Ryan RM]]
		+	[[Category: Sobti M]]
		+	[[Category: Stewart AG]]

OCA at 04:53, 2 September 2020

OCA — Wed, 02 Sep 2020 04:53:08 GMT

←Older revision		Revision as of 04:53, 2 September 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.		Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.

OCA at 09:20, 29 July 2020

OCA — Wed, 29 Jul 2020 09:20:25 GMT

←Older revision		Revision as of 09:20, 29 July 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.		Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.

-	Description: Cryo-EM structure of GltPh L152C-G351C mutant ~~cross-linked with divalent mercury~~ in the intermediate state.	+	Description: Cryo-EM structure of GltPh L152C-G351C mutant in the intermediate outward-facing state.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Sobti, M]]
-	[[Category: Chen, I]]
	[[Category: Font, J]]		[[Category: Font, J]]
	[[Category: Stewart, A.G]]		[[Category: Stewart, A.G]]
		+	[[Category: Sobti, M]]
		+	[[Category: Chen, I]]
	[[Category: Ryan, R.M]]		[[Category: Ryan, R.M]]

OCA at 04:45, 27 May 2020

OCA — Wed, 27 May 2020 04:45:24 GMT

←Older revision		Revision as of 04:45, 27 May 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.		Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.

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

OCA — Wed, 20 May 2020 04:22:26 GMT

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

←Older revision

Revision as of 04:22, 20 May 2020

OCA: New page: '''Unreleased structure''' The entry 6wyl is ON HOLD Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M. Description: Cryo-EM structure of GltPh L152C-G351C mutant cross-...

OCA — Wed, 20 May 2020 04:22:25 GMT

New page: '''Unreleased structure''' The entry 6wyl is ON HOLD Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M. Description: Cryo-EM structure of GltPh L152C-G351C mutant cross-...

New page

'''Unreleased structure'''

The entry 6wyl is ON HOLD

Authors: Font, J., Chen, I., Sobti, M., Stewart, A.G., Ryan, R.M.

Description: Cryo-EM structure of GltPh L152C-G351C mutant cross-linked with divalent mercury in the intermediate state.
[[Category: Unreleased Structures]]
[[Category: Sobti, M]]
[[Category: Chen, I]]
[[Category: Font, J]]
[[Category: Stewart, A.G]]
[[Category: Ryan, R.M]]