Conformational dynamics of the αM3 transmembrane helix during acetylcholine receptor channel gating
Conformational dynamics of the αM3 transmembrane helix during acetylcholine receptor channel gating
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DOI：
10.1529/biophysj.107.105171
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Auerbach, Anthony
中科院分区：
文献类型：
--
作者：
Cadugan, David J.;Auerbach, Anthony
肌肉乙酰胆碱受体是突触离子通道，在闭合通道和开放通道构象之间“门控”。我们使用Phi值分析来探测肌肉乙酰胆碱受体α亚基的跨膜螺旋M3中的残基的双门控反应的过渡态。Phi（1和0之间的分数）参数化突变改变打开相对于关闭速率常数的程度，并且对于线性反应机制，Phi值越高，门控运动“越早”。在α M3的上半部分，所有5个测试残基的门控运动在时间上相关（Phi约为0.30），并用于连接M2中间发生的结构变化，孔衬螺旋与细胞外和跨膜结构域界面发生的结构变化。α M3属于一组复杂而多样的同步运动部件，它们在通道开放过程中相对较晚地改变结构。门控布朗构象级联的传播在跨膜结构域中具有复杂的空间分布。
Muscle acetylcholine receptors are synaptic ion channels that "gate'' between closed- and open-channel conformations. We used Phi-value analysis to probe the transition state of the diliganded gating reaction with regard to residues in the M3, membrane-spanning helix of the muscle acetylcholine receptor alpha-subunit. Phi (a fraction between 1 and 0) parameterizes the extent to which a mutation changes the opening versus the closing rate constant and, for a linear reaction mechanism, the higher the Phi-value, the "earlier'' the gating motion. In the upper half of alpha M3 the gating motions of all five tested residues were temporally correlated (Phi approximate to 0.30) and serve to link structural changes occurring at the middle of the M2, pore-lining helix with those occurring at the interface of the extracellular and transmembrane domains. alpha M3 belongs to a complex and diverse set of synchronously moving parts that change structure relatively late in the channel-opening process. The propagation of the gating Brownian conformational cascade has a complex spatial distribution in the transmembrane domain.