Cooperative nature of gating transitions in K(+) channels as seen from dynamic importance sampling calculations.
Cooperative nature of gating transitions in K(+) channels as seen from dynamic importance sampling calculations.
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DOI：
10.1002/prot.22632
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发表时间：
2010-04
影响因子：
2.9
通讯作者：
Woolf, Thomas B.
中科院分区：
文献类型：
--
作者：
Denning, Elizabeth J.;Woolf, Thomas B.
不断增长的K+通道x射线结构数据集为开始对电压依赖性门控的详细分子理解提供了极好的机会。这些结构虽然顺序不同，但代表稳定的开放状态或封闭状态。然而，要了解门控的分子细节，需要建立过渡模型，并通过实验对门控过渡进行可测试的预测。为了探索这些想法，我们将动态重要性采样（DIMS）应用于四组不同序列和八种不同状态下K+通道分子构象的一组同源模型。在我们的结果中，我们强调了PVP区域上游特定残基对门控转变的重要性。这支持了越来越多的证据，即PVP区域对于影响S6螺旋的柔韧性和门控域的打开是重要的。结果进一步表明，分子水平上的门控如何依赖于亚基内运动来影响K+通道中所有四个亚基的合作行为。我们假设门控过程是分步骤发生的：首先是侧链运动，然后是S5-S6亚基之间的运动，最后是大规模的结构域重排。
The growing dataset of K+ channel x-ray structures provides an excellent opportunity to begin a detailed molecular understanding of voltage-dependent gating. These structures, while differing in sequence, represent either a stable open or closed state. However, an understanding of the molecular details of gating will require models for the transitions and experimentally testable predictions for the gating transition. To explore these ideas, we apply Dynamic Importance Sampling (DIMS) to a set of homology models for the molecular conformations of K+ channels for four different sets of sequences and eight different states. In our results, we highlight the importance of particular residues upstream from the PVP region to the gating transition. This supports growing evidence that the PVP region is important for influencing the flexibility of the S6 helix and thus the opening of the gating domain. The results further suggest how gating on the molecular level depends on intra-subunit motions to influence the cooperative behavior of all four subunits of the K+ channel. We hypothesize that the gating process occurs in steps: first sidechain movement, then inter- S5-S6 subunit motions, and lastly the large-scale domain rearrangements.
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影响因子：
4.3
作者：
Ho BK;Agard DA
通讯作者：
Agard DA
DOI：
10.1085/jgp.118.2.157
发表时间：
2001-08
期刊：
The Journal of general physiology
影响因子：
--
作者：
通讯作者：
--
研究振荡器钾通道中推定的甘氨酸铰链。
影响因子：
3.8
作者：
Ding, Shinghua;Ingleby, Lindsey;Ahern, Christopher A;Horn, Richard
通讯作者：
Horn, Richard
影响因子：
3
作者：
Feig, M;Onufriev, A;Brooks, CL
通讯作者：
Brooks, CL
影响因子：
4.4
作者：
Compoint, M;Picaud, F;Girardet, C
通讯作者：
Girardet, C