Electrostatics studies and molecular dynamics simulations of a homology model of the Shaker K+ channel pore

被引:22
作者
Ranatunga, KM [1 ]
Law, RJ [1 ]
Smith, GR [1 ]
Sansom, MSP [1 ]
机构
[1] Univ Oxford, Dept Biochem, Lab Mol Biophys, Oxford OX1 3QU, England
来源
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS | 2001年 / 30卷 / 04期
基金
英国医学研究理事会; 英国惠康基金;
关键词
potassium channel; Shaker; pK(A) calculation; electrostatics; molecular dynamics;
D O I
10.1007/s002490100134
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
A homology model of the pore domain of the Shaker K+ channel has been constructed using a bacterial K+ channel, KcsA, as a template structure. The model is in agreement with mutagenesis and sequence variability data. A number of structural features are conserved between the two channels, including a ring of tryptophan sidechains on the outer surface of the pore domain at the extracellular end of the helix bundle, and rings of acidic sidechains close to the extracellular mouth of the channel. One of these rings, that formed by four Asp447 sidechains at the mouth of the Shaker pore, is shown by pK(A) calculations to be incompletely ionized at neutral pH. The potential energy profile for a K+ ion moved along the central axis of the Shaker pore domain model selectivity filter reveals a shallow well, the depth of which is modulated by the ionization state of the Asp447 ring. This is more consistent with the high cation flux exhibited by the channel in its conductance value of 19 pS.
引用
收藏
页码:295 / 303
页数:9
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