6bgi - Revision history

OCA at 14:22, 13 March 2024

2024-03-13T14:22:05Z

←Older revision		Revision as of 14:22, 13 March 2024
Line 3:		Line 3:
	<SX load='6bgi' size='340' side='right' viewer='molstar' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>		<SX load='6bgi' size='340' side='right' viewer='molstar' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6BGI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BGI FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 3.8Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[6bgj\|6bgj]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~"><~~b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">Ano1, Tmem16a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])~~</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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [https://pdbe.org/6bgi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [https://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi ProSAT]</span></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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [~~http~~://pdbe.org/6bgi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ANO1_MOUSE ANO1_MOUSE]] Calcium-activated chloride channel (CaCC) which plays an important role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.<ref>PMID:18585372</ref> <ref>PMID:18724360</ref> <ref>PMID:21908539</ref> <ref>PMID:22002868</ref> <ref>PMID:22075693</ref>	+	[https://www.uniprot.org/uniprot/ANO1_MOUSE ANO1_MOUSE] Calcium-activated chloride channel (CaCC) which plays an important role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.<ref>PMID:18585372</ref> <ref>PMID:18724360</ref> <ref>PMID:21908539</ref> <ref>PMID:22002868</ref> <ref>PMID:22075693</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy. Here we present de novo atomic structures of the transmembrane domains of mouse TMEM16A in nanodiscs and in lauryl maltose neopentyl glycol as determined by single-particle electron cryo-microscopy. These structures reveal the ion permeation pore and represent different functional states. The structure in lauryl maltose neopentyl glycol has one Ca(2+) ion resolved within each monomer with a constricted pore; this is likely to correspond to a closed state, because a CaCC with a single Ca(2+) occupancy requires membrane depolarization in order to open (C.J.P. et al., manuscript submitted). The structure in nanodiscs has two Ca(2+) ions per monomer and its pore is in a closed conformation; this probably reflects channel rundown, which is the gradual loss of channel activity that follows prolonged CaCC activation in 1 mM Ca(2+). Our mutagenesis and electrophysiological studies, prompted by analyses of the structures, identified ten residues distributed along the pore that interact with permeant anions and affect anion selectivity, as well as seven pore-lining residues that cluster near pore constrictions and regulate channel gating. Together, these results clarify the basis of CaCC anion conduction.	+
-		+
-	Cryo-EM structures of the TMEM16A calcium-activated chloride channel.,Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbuhler K, Ye W, Qi L, Chen T, Craik CS, Nung Jan Y, Minor DL Jr, Cheng Y, Yeh Jan L Nature. 2017 Dec 13. pii: nature25024. doi: 10.1038/nature25024. PMID:29236684<ref>PMID:29236684</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6bgi" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 15:
	</SX>		</SX>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Bulkley, D]]	+	[[Category: Bulkley D]]
-	[[Category: Chen, T]]	+	[[Category: Chen T]]
-	[[Category: Cheng, Y]]	+	[[Category: Cheng Y]]
-	[[Category: Craik~~, C S~~]]	+	[[Category: Craik CS]]
-	[[Category: Dang, S]]	+	[[Category: Dang S]]
-	[[Category: Feng, S]]	+	[[Category: Feng S]]
-	[[Category: Jan~~, L Y~~]]	+	[[Category: Jan LY]]
-	[[Category: Jan~~, Y N~~]]	+	[[Category: Jan YN]]
-	[[Category: Lolicato, M]]	+	[[Category: Lolicato M]]
-	[[Category: Minor~~, D L~~]]	+	[[Category: Minor Jr DL]]
-	[[Category: Peters~~, C J~~]]	+	[[Category: Peters CJ]]
-	[[Category: Qi, J]]	+	[[Category: Qi J]]
-	[[Category: Tien, J]]	+	[[Category: Tien J]]
-	[[Category: Ye, W]]	+	[[Category: Ye W]]
-	[[Category: Zhao, J]]	+	[[Category: Zhao J]]
-	[[Category: Zuberbuhler, K]]	+	[[Category: Zuberbuhler K]]
-	~~[[Category: Chloride channel]]~~	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Tmem16 family~~]]	+

OCA at 23:22, 10 April 2020

2020-04-10T23:22:24Z

←Older revision		Revision as of 23:22, 10 April 2020
Line 3:		Line 3:
	<SX load='6bgi' size='340' side='right' viewer='molstar' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>		<SX load='6bgi' size='340' side='right' viewer='molstar' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BGI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BGI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bgj\|6bgj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bgj\|6bgj]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ano1, Tmem16a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ano1, Tmem16a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [http://pdbe.org/6bgi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [http://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi ProSAT]</span></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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [http://pdbe.org/6bgi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [http://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 20:31, 6 March 2020

2020-03-06T20:31:34Z

←Older revision		Revision as of 20:31, 6 March 2020
Line 1:		Line 1:

	==Cryo-EM structure of the TMEM16A calcium-activated chloride channel in nanodisc==		==Cryo-EM structure of the TMEM16A calcium-activated chloride channel in nanodisc==
-	<~~StructureSection~~ load='6bgi' size='340' side='right'caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>	+	<SX load='6bgi' size='340' side='right' viewer='molstar' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>		<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>
Line 23:		Line 23:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]

OCA at 09:52, 4 December 2019

2019-12-04T09:52:16Z

←Older revision		Revision as of 09:52, 4 December 2019
Line 1:		Line 1:

	==Cryo-EM structure of the TMEM16A calcium-activated chloride channel in nanodisc==		==Cryo-EM structure of the TMEM16A calcium-activated chloride channel in nanodisc==
-	<StructureSection load='6bgi' size='340' side='right' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>	+	<StructureSection load='6bgi' size='340' side='right'caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>		<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>
Line 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Bulkley, D]]		[[Category: Bulkley, D]]

OCA at 08:43, 10 January 2018

2018-01-10T08:43:22Z

←Older revision		Revision as of 08:43, 10 January 2018
Line 3:		Line 3:
	<StructureSection load='6bgi' size='340' side='right' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>		<StructureSection load='6bgi' size='340' side='right' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bgj\|6bgj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bgj\|6bgj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ano1, Tmem16a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [http://pdbe.org/6bgi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [http://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi 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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [http://pdbe.org/6bgi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [http://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Bulkley, D]]		[[Category: Bulkley, D]]
	[[Category: Chen, T]]		[[Category: Chen, T]]

OCA at 08:38, 27 December 2017

2017-12-27T08:38:45Z

←Older revision		Revision as of 08:38, 27 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6bgi is ~~ON HOLD~~	+	==Cryo-EM structure of the TMEM16A calcium-activated chloride channel in nanodisc==
		+	<StructureSection load='6bgi' size='340' side='right' caption='[[6bgi]], [[Resolution\|resolution]] 3.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6bgi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6bgj\|6bgj]]</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=6bgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgi OCA], [http://pdbe.org/6bgi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgi RCSB], [http://www.ebi.ac.uk/pdbsum/6bgi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgi ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ANO1_MOUSE ANO1_MOUSE]] Calcium-activated chloride channel (CaCC) which plays an important role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.<ref>PMID:18585372</ref> <ref>PMID:18724360</ref> <ref>PMID:21908539</ref> <ref>PMID:22002868</ref> <ref>PMID:22075693</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy. Here we present de novo atomic structures of the transmembrane domains of mouse TMEM16A in nanodiscs and in lauryl maltose neopentyl glycol as determined by single-particle electron cryo-microscopy. These structures reveal the ion permeation pore and represent different functional states. The structure in lauryl maltose neopentyl glycol has one Ca(2+) ion resolved within each monomer with a constricted pore; this is likely to correspond to a closed state, because a CaCC with a single Ca(2+) occupancy requires membrane depolarization in order to open (C.J.P. et al., manuscript submitted). The structure in nanodiscs has two Ca(2+) ions per monomer and its pore is in a closed conformation; this probably reflects channel rundown, which is the gradual loss of channel activity that follows prolonged CaCC activation in 1 mM Ca(2+). Our mutagenesis and electrophysiological studies, prompted by analyses of the structures, identified ten residues distributed along the pore that interact with permeant anions and affect anion selectivity, as well as seven pore-lining residues that cluster near pore constrictions and regulate channel gating. Together, these results clarify the basis of CaCC anion conduction.

-	~~Authors~~:	+	Cryo-EM structures of the TMEM16A calcium-activated chloride channel.,Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbuhler K, Ye W, Qi L, Chen T, Craik CS, Nung Jan Y, Minor DL Jr, Cheng Y, Yeh Jan L Nature. 2017 Dec 13. pii: nature25024. doi: 10.1038/nature25024. PMID:29236684<ref>PMID:29236684</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6bgi" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bulkley, D]]
		+	[[Category: Chen, T]]
		+	[[Category: Cheng, Y]]
		+	[[Category: Craik, C S]]
		+	[[Category: Dang, S]]
		+	[[Category: Feng, S]]
		+	[[Category: Jan, L Y]]
		+	[[Category: Jan, Y N]]
		+	[[Category: Lolicato, M]]
		+	[[Category: Minor, D L]]
		+	[[Category: Peters, C J]]
		+	[[Category: Qi, J]]
		+	[[Category: Tien, J]]
		+	[[Category: Ye, W]]
		+	[[Category: Zhao, J]]
		+	[[Category: Zuberbuhler, K]]
		+	[[Category: Chloride channel]]
		+	[[Category: Membrane protein]]
		+	[[Category: Tmem16 family]]

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

2017-11-08T06:34:03Z

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

←Older revision

Revision as of 06:34, 8 November 2017

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

2017-11-08T06:34:02Z

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

New page

'''Unreleased structure'''

The entry 6bgi is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]