title: Voltage sensor ring in a native structure of a membrane-embedded potassium channel.
abstract: Voltage-gated ion channels support electrochemical activity in cells and are largely responsible for information flow throughout the nervous systems. The voltage sensor domains in these channels sense changes in transmembrane potential and control ion flux across membranes. The X-ray structures of a few voltage-gated ion channels in detergents have been determined and have revealed clear structural variations among their respective voltage sensor domains. More recent studies demonstrated that lipids around a voltage-gated channel could directly alter its conformational state in membrane. Because of these disparities, the structural basis for voltage sensing in native membranes remains elusive. Here, through electron-crystallographic analysis of membrane-embedded proteins, we present the detailed view of a voltage-gated potassium channel in its inactivated state. Contrary to all known structures of voltage-gated ion channels in detergents, our data revealed a unique conformation in which the four voltage sensor domains of a voltage-gated potassium channel from Aeropyrum pernix (KvAP) form a ring structure that completely surrounds the pore domain of the channel. Such a structure is named the voltage sensor ring. Our biochemical and electrophysiological studies support that the voltage sensor ring represents a physiological conformation. These data together suggest that lipids exert strong effects on the channel structure and that these effects may be changed upon membrane disruption. Our results have wide implications for lipid-protein interactions in general and for the mechanism of voltage sensing in particular.
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Liang
authors: L
authors: Shi
authors: Hongjin
authors: H
authors: Zheng
authors: Hui
authors: H
authors: Zheng
authors: Brian A
authors: BA
authors: Borkowski
authors: Dan
authors: D
authors: Shi
authors: Tamir
authors: T
authors: Gonen
authors: Qiu-Xing
authors: QX
authors: Jiang
mesh_terms: D041522:Aeropyrum / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D018360:Crystallography, X-Ray; D004583:Electrons; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D003432:Cross-Linking Reagents; D008055:Lipids; D024642:Potassium Channels, Voltage-Gated
references: Nature. 2006 Apr 27;440(7088):1213-6
references: 16554753
references: J Biol Chem. 2002 Nov 8;277(45):42719-25
references: 12196543
references: Science. 2004 Oct 15;306(5695):491-5
references: 15486302
references: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1511-5
references: 18216238
references: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
references: 20383002
references: Nature. 2005 Dec 1;438(7068):633-8
references: 16319884
references: Protein Sci. 2008 Mar;17(3):506-17
references: 18287283
references: Nature. 2005 Jun 30;435(7046):1239-43
references: 15902207
references: Nature. 2004 Aug 12;430(7001):806-10
references: 15306816
references: Science. 2010 Apr 2;328(5974):67-73
references: 20360102
references: J Gen Physiol. 1998 Feb;111(2):313-42
references: 9450946
references: Q Rev Biophys. 1994 Feb;27(1):1-40
references: 7520590
references: Nature. 1990 Jun 21;345(6277):672
references: 1694264
references: Nat Commun. 2011;2:250
references: 21427721
references: Nature. 2012 May 20;486(7401):130-4
references: 22678295
references: Neuron. 2008 Jul 10;59(1):98-109
references: 18614032
references: Nature. 2005 Aug 11;436(7052):848-51
references: 16094368
references: Nature. 2008 Dec 18;456(7224):891-7
references: 19092925
references: Nature. 1975 Sep 4;257(5521):28-32
references: 1161000
references: Structure. 2008 Mar;16(3):398-409
references: 18334215
references: Biochem Biophys Res Commun. 2010 Aug 27;399(3):341-6
references: 20655880
references: J Mol Biol. 1998 Sep 18;282(2):211-6
references: 9735281
references: Nature. 2003 May 1;423(6935):42-8
references: 12721619
references: Nature. 2003 Mar 13;422(6928):180-5
references: 12629550
references: Nature. 2011 Jul 10;475(7356):353-8
references: 21743477
references: Eur Biophys J. 2011 Jun;40(6):783-93
references: 21455829
references: Biophys J. 1994 Apr;66(4):1061-7
references: 8038378
references: Neuron. 1995 Jun;14(6):1293-301
references: 7605638
references: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15441-6
references: 16223877
references: Cell. 2005 Nov 4;123(3):463-75
references: 16269337
references: J Physiol. 1952 Apr;116(4):424-48
references: 14946712
references: EMBO J. 2004 Dec 8;23(24):4717-26
references: 15565171
references: J Mol Biol. 2008 Sep 26;382(1):24-33
references: 18638484
references: Physiol Rev. 2000 Apr;80(2):555-92
references: 10747201
references: Prog Biophys Mol Biol. 1982;39(3):183-231
references: 6289376
references: Science. 1991 May 24;252(5009):1092-6
references: 2031183
references: Nature. 2008 Feb 14;451(7180):826-9
references: 18273018
references: Nature. 2006 Dec 7;444(7120):775-9
references: 17136096
references: J Mol Biol. 1990 Jun 20;213(4):899-929
references: 2359127
references: Curr Opin Struct Biol. 2012 Aug;22(4):529-36
references: 22483432
references: Nature. 2003 May 1;423(6935):33-41
references: 12721618
references: Nature. 2007 Nov 15;450(7168):376-82
references: 18004376
references: Nature. 2007 Feb 1;445(7127):550-3
references: 17187053
references: J Physiol. 1952 Aug;117(4):500-44
references: 12991237
references: PLoS One. 2008 Apr 09;3(4):e1935
references: 18398461
references: Nature. 2012 May 20;486(7401):135-9
references: 22678296
references: J Gen Physiol. 1994 Feb;103(2):321-62
references: 8189208
references: Science. 2006 Apr 28;312(5773):589-92
references: 16556803