Coupled motions between pore and voltage-sensor domains:: A model for Shaker B, a voltage-gated potassium channel

被引:34
作者
Treptow, W [1 ]
Maigret, B [1 ]
Chipot, C [1 ]
Tarek, M [1 ]
机构
[1] Univ Brasilia, Dept Biol Celular, Brasilia, DF, Brazil
关键词
D O I
10.1529/biophysj.104.039628
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
A high-resolution crystal structure of KvAP, an archeabacterial voltage-gated potassium (Kv) channel, complexed with a monoclonal Fab fragment has been recently determined. Based on this structure, a mechanism for the activation ( opening) of Kv channels has been put forward. This mechanism has since been criticized, suggesting that the resolved structure is not representative of the family of voltage-gated potassium channels. Here, we propose a model of the transmembrane domain of Shaker B, a well-characterized Kv channel, built by homology modeling and docking calculations. In this model, the positively charged S4 helices are oriented perpendicular to the membrane and localized in the groove between segments S5 and S6 of adjacent subunits. The structure and the dynamics of the full atomistic model embedded in a hydrated lipid bilayer were investigated by means of two large-scale molecular dynamics simulations under transmembrane-voltage conditions known to induce, respectively, the resting state ( closed) and the activation ( opening) of voltage-gated channels. Upon activation, the model undergoes conformational changes that lead to an increase of the hydration of the charged S4 helices, correlated with an upward translation and a tilting of the latter, concurrently with movements of the S5 helices and the activation gate. Although small, these conformational changes ultimately result in an alteration of the ion-conduction pathway. Our findings support the transporter model devised by Bezanilla and collaborators, and further underline the crucial role played by internal hydration in the activation of the channel.
引用
收藏
页码:2365 / 2379
页数:15
相关论文
共 93 条
[1]   Specificity of charge-carrying residues in the voltage sensor of potassium channels [J].
Ahern, CA ;
Horn, R .
JOURNAL OF GENERAL PHYSIOLOGY, 2004, 123 (03) :205-216
[2]   ESSENTIAL DYNAMICS OF PROTEINS [J].
AMADEI, A ;
LINSSEN, ABM ;
BERENDSEN, HJC .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 17 (04) :412-425
[3]  
[Anonymous], 1992, Ionic Channels of Excitable Membranes Sunderland
[4]   Ion permeation mechanism of the potassium channel [J].
Åqvist, J ;
Luzhkov, V .
NATURE, 2000, 404 (6780) :881-884
[5]   Ion channel gating: insights via molecular simulations [J].
Beckstein, O ;
Biggin, PC ;
Bond, P ;
Bright, JN ;
Domene, C ;
Grottesi, A ;
Holyoake, J ;
Sansom, MSP .
FEBS LETTERS, 2003, 555 (01) :85-90
[6]   Changes in local S4 environment provide a voltage-sensing mechanism for mammalian hyperpolarization-activated HCN channels [J].
Bell, DC ;
Yao, H ;
Saenger, RC ;
Riley, JH ;
Siegelbaum, SA .
JOURNAL OF GENERAL PHYSIOLOGY, 2004, 123 (01) :5-19
[7]   Molecular dynamics of the KcsA K+ channel in a bilayer membrane [J].
Bernèche, S ;
Roux, B .
BIOPHYSICAL JOURNAL, 2000, 78 (06) :2900-2917
[8]   A microscopic view of ion conduction through the K+ channel [J].
Bernèche, S ;
Roux, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (15) :8644-8648
[9]   The voltage sensor in voltage-dependent ion channels [J].
Bezanilla, F .
PHYSIOLOGICAL REVIEWS, 2000, 80 (02) :555-592
[10]   Perspective - Voltage sensor movements [J].
Bezanilla, F .
JOURNAL OF GENERAL PHYSIOLOGY, 2002, 120 (04) :465-473