State-dependent block of BK channels by synthesized shaker ball peptides.
State-dependent block of BK channels by synthesized shaker ball peptides.
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DOI：
10.1085/jgp.200609521
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发表时间：
2006-10
期刊：
影响因子：
--
通讯作者：
Aldrich RW
中科院分区：
文献类型：
--
作者：
Li W;Aldrich RW
钾离子通道的晶体结构有力地证实了早期基于功能研究的假设，即通道门位于孔的细胞质侧。然而，对几种类型的配体敏感性K+通道的可及性研究表明，它们的激活门可能位于选择性过滤器附近或内部。在多大程度上栅极的物理位置在大的K+沟道家族中是保守的，这还有待确定。关于大电导钙激活钾通道（BK）门控位置的直接证据很少，BK通道由电压和配体（钙）门控。我们早期的动力学测量BK通道的内部季铵离子的块提出了可能性，他们可能缺乏一个细胞质门。在这项研究中，我们表明，合成的Shaker球肽（ShBP）同系物作为BK通道的状态依赖性阻滞剂时，内部应用，这表明门控时在通道孔的细胞内端加宽。这是一致的门控相关的构象变化，在细胞质端的孔内衬螺旋，所建议的其他K+通道的功能和结构的研究。此外，我们从两个BK通道突变的结果表明，类似类型的球肽和通道之间的相互作用是由BK和其他K+通道类型共享。
Crystal structures of potassium channels have strongly corroborated an earlier hypothetical picture based on functional studies, in which the channel gate was located on the cytoplasmic side of the pore. However, accessibility studies on several types of ligand-sensitive K+ channels have suggested that their activation gates may be located near or within the selectivity filter instead. It remains to be determined to what extent the physical location of the gate is conserved across the large K+ channel family. Direct evidence about the location of the gate in large conductance calcium-activated K+ (BK) channels, which are gated by both voltage and ligand (calcium), has been scarce. Our earlier kinetic measurements of the block of BK channels by internal quaternary ammonium ions have raised the possibility that they may lack a cytoplasmic gate. We show in this study that a synthesized Shaker ball peptide (ShBP) homologue acts as a state-dependent blocker for BK channels when applied internally, suggesting a widening at the intracellular end of the channel pore upon gating. This is consistent with a gating-related conformational change at the cytoplasmic end of the pore-lining helices, as suggested by previous functional and structural studies on other K+ channels. Furthermore, our results from two BK channel mutations demonstrate that similar types of interactions between ball peptides and channels are shared by BK and other K+ channel types.
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DOI：
10.1085/jgp.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
DOI：
10.1085/jgp.59.4.388
发表时间：
1972-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Armstrong CM;Hille B
通讯作者：
Hille B
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
内部BA2+与平滑肌的克隆Ca（2+） - 依赖性K+（HSLO）通道的相互作用。
影响因子：
3.8
作者：
Diaz, F;Wallner, M;Stefani, E;Toro, L;Latorre, R
通讯作者：
Latorre, R
影响因子：
3.8
作者：
Holmgren, M;Smith, PL;Yellen, G
通讯作者：
Yellen, G