Structural dynamics of the M4 transmembrane segment during acetylcholine receptor gating
Structural dynamics of the M4 transmembrane segment during acetylcholine receptor gating
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DOI：
10.1016/j.str.2004.08.004
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发表时间：
2004-10-01
期刊：
影响因子：
5.7
通讯作者：
Auerbach, AL
中科院分区：
文献类型：
--
作者：
Mitra, A;Bailey, TD;Auerbach, AL
连接变构蛋白稳定末端状态的过渡态结构在很大程度上尚未解决。我们使用单分子动力学分析，以探测M4跨膜段的动力学过程中的封闭可逆箭头开放异构化的神经肌肉乙酰胆碱受体离子通道（AChR）。我们测量了87个突变体的自由能关系的斜率（φ），这揭示了突变残基在过渡态的开放与封闭的特征，因此门控分子运动的序列和组织。φ在α亚基M4片段的整个长度上是恒定的，平均值为0.54，表明该结构域作为一个单元移动，大约在反应的中途。对杂交构建体的分析表明，两个α亚基同步移动。在亚基之间，M4运动的顺序是α-β-β。AChR离子通道作为具有许多移动部件的动态纳米机器出现。
The transition state structures that link the stable end states of allosteric proteins are largely unresolved. We used single-molecule kinetic analysis to probe the dynamics of the M4 transmembrane segments during the closed reversible arrow open isomerization of the neuromuscular acetylcholine receptor ion channel (AChR). We measured the slopes (phi) of the free energy relationships for 87 mutants, which reveal the open-versus closed-like characters of the mutated residues at the transition state and hence the sequence and organization of gating molecular motions. phi was constant throughout the length of the a subunit M4 segment with an average value of 0.54, suggesting that this domain moves as a unit, approximately midway through the reaction. Analysis of a hybrid construct indicates that the two alpha subunits move synchronously. Between subunits, the sequence of M4 motions is alpha-epsilon-beta. The AChR ion channel emerges as a dynamic nanomachine with many moving parts.