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Time-resolved measurements of an ion channel conformational change driven by a membrane phase transition
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2017-09-25 00:00:00 , DOI: 10.1073/pnas.1708070114
Paul Stevenson 1, 2, 3, 4 , Andrei Tokmakoff 2, 3, 4
Affiliation  

Using temperature-jump infrared spectroscopy, we are able to trigger a gel-to-fluid phase transition in lipid vesicles and monitor in real time how a membrane protein responds to structural changes in the membrane. The melting of lipid domains in 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles is observed to occur in as fast as 50 ns, with a temperature dependence characteristic of critical slowing. Gramicidin D (gD) added to the membrane responds primarily to the change in thickness of the membrane on a timescale coincident with the membrane melting. Using structure-based spectral modeling, we assign the conformational changes to compression and rotation of a partially dissociated gD dimer. Free energy calculations indicate that the high rate is a result of near-barrierless diffusion on a protein energy landscape that is radically reshaped by membrane thinning. The structural changes associated with the phase transition are similar to the fluctuation modes of fluid phase membranes, highlighting the importance of understanding the dynamic nature of the membrane environment around proteins.

中文翻译:

膜相变驱动的离子通道构象变化的时间分辨测量

使用温度跃变红外光谱,我们能够触发脂质囊泡中的凝胶到流体的相变,并实时监控膜蛋白如何响应膜中的结构变化。观察到在1,2-二肉豆蔻酰基-sn-甘油-3-磷酸胆碱囊泡中的脂质结构域的熔化最快可在50 ns内发生,并具有临界减慢的温度依赖性。在与膜融化相一致的时间尺度上,添加到膜中的格拉米霉素D(gD)主要对膜厚度的变化作出反应。使用基于结构的光谱建模,我们将构象变化分配给部分解离的gD二聚体的压缩和旋转。自由能计算表明,高速率是蛋白质能量格局上几乎无障碍扩散的结果,该态势通过膜变薄而彻底重塑。与相变相关的结构变化类似于液相膜的波动模式,突出了理解蛋白质周围膜环境动态性质的重要性。
更新日期:2017-09-26
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