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通过开放通道电流噪声分析研究短杆菌肽A跨膜通道的分子动力学

Molecular dynamics of alamethicin transmembrane channels from open-channel current noise analysis.

作者信息

Mak D O, Webb W W

机构信息

Physics Department, Cornell University, Ithaca, New York 14853, USA.

出版信息

Biophys J. 1995 Dec;69(6):2337-49. doi: 10.1016/S0006-3495(95)80103-7.

DOI:10.1016/S0006-3495(95)80103-7
PMID:8599640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1236471/
Abstract

Conductance noise measurement of the open states of alamethicin transmembrane channels reveals excess noise attributable to cooperative low-frequency molecular dynamics that can generate fluctuations approximately 1 A rms in the effective channel pore radius. Single-channel currents through both persistent and nonpersistent channels with multiple conductance states formed by purified polypeptide alamethicin in artificial phospholipid bilayers isolated onto micropipettes with gigaohm seals were recorded using a voltage-clamp technique with low background noise (rms noise < 3 pA up to 20 kHz). Current noise power spectra between 100 Hz and 20 kHz of each open channel state showed little frequency dependence. Noise from undetected conductance state transitions was insignificant. Johnson and shot noises were evaluated. Current noise caused by electrolyte concentration fluctuation via diffusion was isolated by its dependence on buffer concentration. After removing these contributions, significant current noise remains in all persistent channel states and increases in higher conductance states. In nonpersistent channels, remaining noise occurs primarily in the lowest two states. These fluctuations of channel conductance are attributed to thermal oscillations of the channel molecular conformation and are modeled as a Langevin translational oscillation of alamethicin molecules moving radially from the channel pore, damped mostly by lipid bilayer viscosity.

摘要

对短杆菌肽跨膜通道开放状态的电导噪声测量表明,存在过量噪声,这归因于协同低频分子动力学,该动力学可在有效通道孔径半径中产生约1埃均方根(rms)的波动。使用具有低背景噪声(高达20 kHz时均方根噪声<3 pA)的电压钳技术,记录了通过由纯化的多肽短杆菌肽在人工磷脂双层中形成的具有多种电导状态的持续和非持续通道的单通道电流,这些人工磷脂双层被隔离在具有千兆欧密封的微吸管上。每个开放通道状态在100 Hz至20 kHz之间的电流噪声功率谱显示出几乎没有频率依赖性。未检测到的电导状态转变产生的噪声微不足道。对约翰逊噪声和散粒噪声进行了评估。通过其对缓冲液浓度的依赖性,分离了由电解质浓度通过扩散波动引起的电流噪声。去除这些贡献后,所有持续通道状态中仍存在显著的电流噪声,并且在更高电导状态下增加。在非持续通道中,剩余噪声主要出现在最低的两个状态。通道电导的这些波动归因于通道分子构象的热振荡,并被建模为短杆菌肽分子从通道孔径向移动的朗之万平移振荡,主要由脂质双层粘度阻尼。

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本文引用的文献

1
Alamethicin and related peptaibols--model ion channels.短杆菌肽A及相关肽抗生素——离子通道模型
Eur Biophys J. 1993;22(2):105-24. doi: 10.1007/BF00196915.
2
Structural fluctuations between two conformational states of a transmembrane helical peptide are related to its channel-forming properties in planar lipid membranes.跨膜螺旋肽的两种构象状态之间的结构波动与其在平面脂质膜中的通道形成特性相关。
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Dynamics of proteins: elements and function.蛋白质动力学:要素与功能
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8
Fluctuations in protein structure from X-ray diffraction.X射线衍射法测定的蛋白质结构波动
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Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.用于从细胞和无细胞膜片进行高分辨率电流记录的改进膜片钳技术。
Pflugers Arch. 1981 Aug;391(2):85-100. doi: 10.1007/BF00656997.
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Voltage-dependent channels in planar lipid bilayer membranes.平面脂质双分子层膜中的电压依赖性通道。
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