Molecular determinants of gating at the potassium-channel selectivity filter

被引:368
作者
Cordero-Morales, JF
Cuello, LG
Zhao, YX
Jogini, V
Cortes, DM
Roux, B
Perozo, E
机构
[1] Univ Chicago, Ctr Integrat Sci, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
[2] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22906 USA
[3] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nsmb1069
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We show that in the potassium channel KcsA, proton-dependent activation is followed by an inactivation process similar to C-type inactivation, and this process is suppressed by an E71A mutation in the pore helix. EPR spectroscopy demonstrates that the inner gate opens maximally at low pH regardless of the magnitude of the single-channel-open probability, implying that stationary gating originates mostly from rearrangements at the selectivity filter. Two E71A crystal structures obtained at 2.5 (A) over circle reveal large structural excursions of the selectivity filter during ion conduction and provide a glimpse of the range of conformations available to this region of the channel during gating. These data establish a mechanistic basis for the role of the selectivity filter during channel activation and inactivation.
引用
收藏
页码:311 / 318
页数:8
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