Dynamics of the Kv1.2 voltage-gated K+ channel in a membrane environment.
All-atom molecular dynamics simulations are used to better understand the dynamic environment experienced by the Kv1.2 channel in a lipid membrane. The structure of the channel is stable during the trajectories. The pore domain keeps a well-defined conformation, whereas the voltage-sensing domains undergo important lateral fluctuations, consistent with their modular nature. A channel-like region at the center of the S1-S4 helical bundle fills rapidly with water, reminiscent of the concept of high-dielectric aqueous crevices. The first two arginines along S4 (R294 and R297) adopt an interfacial position where they interact favorably with water and the lipid headgroups. The following two arginines (R300 and R303) interact predominantly with water and E226 in S2. Despite the absence of a structurally permanent gating pore formed by protein residues and surrounding the S4 helix, as traditionally pictured, the charged residues are located in a favorable environment and are not extensively exposed to the membrane nonpolar region. Continuum electrostatic computations indicate that the transmembrane potential sensed by the charged residues in the voltage sensor varies abruptly over the outer half of the membrane in the arginine-rich region of S4; thus, the voltage gradient or membrane electric field is "focused". Interactions of basic residues with the lipid headgroups at the intracellular membrane-solution interface reduce the membrane thickness near the channel, resulting in an increased transmembrane field.
Jogini
Vishwanath
V
Institute of Molecular Pediatric Sciences, Gordon Center for Integrative Science, The University of Chicago, Chicago, Illinois, USA.
Roux
Benoît
B
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000502:physiology*; D003198:Computer Simulation; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology; D051663:Kv1.2 Potassium Channel / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry / Q000502:physiology; D013816:Thermodynamics
D029721:Drosophila Proteins; D051663:Kv1.2 Potassium Channel; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels
Nature. 2006 Apr 27;440(7088):1213-6
16554753
Neuron. 2003 Jan 9;37(1):85-97
12526775
Q Rev Biophys. 1994 Feb;27(1):1-40
7520590
Neuron. 2007 Oct 4;56(1):124-40
17920020
Neuron. 2005 Feb 3;45(3):379-88
15694325
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11631-5
7526400
FEBS Lett. 2004 Apr 30;564(3):257-63
15111106
Nature. 2002 May 30;417(6888):515-22
12037559
Biophys J. 1997 Dec;73(6):2980-9
9414213
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4943-8
17360368
Science. 2005 Aug 5;309(5736):897-903
16002581
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15059-64
16217012
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9617-23
11493701
Neuron. 1996 Jun;16(6):1169-77
8663993
Neuron. 1996 Jun;16(6):1159-67
8663992
Science. 2005 Aug 5;309(5736):903-8
16002579
Biophys J. 2006 Feb 1;90(3):822-30
16272446
J Gen Physiol. 1999 Mar;113(3):389-414
10051516
Nature. 2003 May 1;423(6935):42-8
12721619
Biophys J. 2001 Apr;80(4):1802-9
11259293
Biochemistry. 2000 Nov 7;39(44):13295-306
11063565
Biophys J. 1994 Apr;66(4):1011-21
8038375
Biophys J. 1992 Feb;61(2):428-33
1547330
Biomembranes. 1975;7:1-9
1092378
Biophys J. 2000 Jun;78(6):2900-17
10827971
Biophys J. 1997 Apr;72(4):1489-500
9083655
Biophys J. 1998 Oct;75(4):1603-18
9746504
Nat Struct Biol. 2000 Apr;7(4):309-11
10742176
Proc Natl Acad Sci U S A. 2007 May 8;104(19):7904-9
17470814
J Phys Chem B. 1998 Apr 30;102(18):3586-616
24889800
Physiol Rev. 2000 Apr;80(2):555-92
10747201
Biophys J. 2006 May 1;90(9):L64-6
16533847
Proteins. 2004 May 1;55(2):223-8
15048815
J Gen Physiol. 2001 Jan;117(1):69-89
11134232
Neuron. 2005 Oct 6;48(1):25-9
16202706
J Gen Physiol. 2000 Jan;115(1):33-50
10613917
Nature. 2006 Dec 7;444(7120):775-9
17136096
Neuron. 2003 Oct 30;40(3):515-25
14642276
J Mol Biol. 1997 Apr 18;267(5):1268-82
9150411
Annu Rev Biophys Biomol Struct. 2002;31:275-302
11988471
J Gen Physiol. 1998 Mar;111(3):399-420
9482708
Nature. 2003 May 1;423(6935):33-41
12721618
Biophys J. 2005 Feb;88(2):1018-29
15556975
Novartis Found Symp. 2002;245:178-90; discussion 190-2, 261-4
12027007
J Gen Physiol. 1999 Mar;113(3):415-23
10051517
Nature. 1999 Dec 16;402(6763):809-13
10617201
J Gen Physiol. 2000 Feb;115(2):123-38
10653892
Nature. 2005 Jun 30;435(7046):1239-43
15902207
J Chem Phys. 2004 Dec 8;121(22):10847-51
15634036
J Gen Physiol. 2001 Mar;117(3):205-18
11222625
Science. 1988 Oct 7;242(4875):50-61
2459775
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2935-40
12606713
Biophys J. 2006 Mar 1;90(5):1598-606
16326912
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17640-5
15591352
Neuron. 2006 Nov 22;52(4):623-34
17114047
Neuron. 2003 Jul 31;39(3):467-81
12895421
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7292-7
16648251
Proc Natl Acad Sci U S A. 1986 Jan;83(2):508-12
2417247
J Mol Biol. 1993 Mar 20;230(2):543-74
8464064
Nature. 2004 Feb 5;427(6974):548-53
14765197
J Biol Chem. 1994 Mar 11;269(10):7185-91
8125930
J Chem Phys. 2006 Oct 14;125(14):144710
17042634
J Gen Physiol. 2000 Jan;115(1):51-8
10613918
Nature. 2005 Aug 11;436(7052):852-6
16094369
Biophys J. 2006 Dec 1;91(11):L90-2
17012321
Nature. 2007 Feb 1;445(7127):546-9
17187057
Biophys J. 1996 Jul;71(1):19-39
8804586
J Gen Physiol. 1994 Feb;103(2):321-62
8189208
Structure. 2004 Jan;12(1):65-74
14725766
Science. 2006 Apr 28;312(5773):589-92
16556803