State-dependent network connectivity determines gating in a K+ channel.
State-dependent network connectivity determines gating in a K+ channel.
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DOI：
10.1016/j.str.2014.04.018
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发表时间：
2014-07-08
期刊：
影响因子：
5.7
通讯作者：
Baukrowitz, Thomas
中科院分区：
文献类型：
--
作者：
Bollepalli, Murali K.;Fowler, Philip W.;Rapedius, Markus;Shang, Lijun;Sansom, Mark S. P.;Tucker, Stephen J.;Baukrowitz, Thomas
X射线晶体学为膜蛋白的不同结构状态提供了巨大的洞察力，特别是离子通道。然而，决定特定状态的热力学稳定性的分子力却知之甚少。在这里，我们分析了不同的X射线结构的内向整流钾通道（Kir1.1）的功能数据，我们获得了超过190个突变体Kir1.1。该诱变扰动分析揭示了物理相互作用残基的广泛的状态依赖性网络，其稳定了通道的预开放和开放状态，但在通道关闭时片段。我们证明，这个门控网络是这些不同的门控状态的热力学稳定性的一个重要的结构决定因素，并确定个别突变对通道功能的影响。这些结果不仅对我们理解K+通道门控，而且对我们理解其他变构蛋白中发生的更普遍的构象转变性质具有重要意义。Kir通道不同晶体状态的功能验证大规模诱变揭示了状态依赖性门控网络的存在由于开放状态不稳定突变对Kir通道门控的偏倚效应由物理连接的残基网络介导的长程变构偶联决定离子通道门控状态热力学稳定性的分子力知之甚少。在这里，Bollepalli等人。表明，一个广泛的状态依赖网络的物理相互作用的残基决定的热力学稳定性的不同门控状态的KIR通道。
X-ray crystallography has provided tremendous insight into the different structural states of membrane proteins and, in particular, of ion channels. However, the molecular forces that determine the thermodynamic stability of a particular state are poorly understood. Here we analyze the different X-ray structures of an inwardly rectifying potassium channel (Kir1.1) in relation to functional data we obtained for over 190 mutants in Kir1.1. This mutagenic perturbation analysis uncovered an extensive, state-dependent network of physically interacting residues that stabilizes the pre-open and open states of the channel, but fragments upon channel closure. We demonstrate that this gating network is an important structural determinant of the thermodynamic stability of these different gating states and determines the impact of individual mutations on channel function. These results have important implications for our understanding of not only K+ channel gating but also the more general nature of conformational transitions that occur in other allosteric proteins. Functional validation of different crystallographic states of Kir channels Presence of a state-dependent gating network revealed by large-scale mutagenesis Biased effect of mutations on Kir channel gating due to open-state destabilization Long-range allosteric coupling mediated by a physically connected residue network The molecular forces that determine the thermodynamic stability of ion channel gating states are poorly understood. Here, Bollepalli et al. show that an extensive state-dependent network of physically interacting residues determines the thermodynamic stability of the different gating states in Kir channels.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
64.8
作者：
Whorton MR;MacKinnon R
通讯作者：
MacKinnon R
影响因子：
16.8
作者：
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--
DOI：
10.1073/pnas.0708120104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Sadovsky, Evgeniya;Yifrach, Ofer
通讯作者：
Yifrach, Ofer
影响因子：
64.8
作者：
Noskov, SY;Bernèche, S;Roux, B
通讯作者：
Roux, B