Intramolecular Diffusion in α-Synuclein: It Depends on How You Measure It.
Intramolecular Diffusion in α-Synuclein: It Depends on How You Measure It.
复制标题
α-突触核蛋白的分子内扩散：这取决于您如何测量它。
DOI：
10.1016/j.bpj.2018.08.023
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发表时间：
2018
影响因子：
3.4
通讯作者：
Lapidus,LisaJ
中科院分区：
文献类型：
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作者：
Woodard,Jaie;Srivastava,KinshukR;Rahamim,Gil;Grupi,Asaf;Hogan,Steven;Witalka,DavidJ;Nawrocki,Grzegorz;Haas,Elisha;Feig,Michael;Lapidus,LisaJ
分子内蛋白质扩散，即多肽链的一部分相对于另一部分的运动，是蛋白质折叠的一个基本方面，可能调节与疾病相关的固有紊乱蛋白质的淀粉样蛋白的形成。许多工作已经使用各种探针来确定这样的扩散系数，但是在使用诸如荧光共振能量转移之类的长程探针和诸如Trp-Cys猝灭之类的短程探针之间存在明显的差异。在这项工作中，我们对同一蛋白质α-突触核蛋白进行了这两种测量，并证实了这种差异的存在。分子动力学模拟表明，这种差异是由扩散系数造成的，扩散系数取决于探针之间的空间距离。考虑到荧光共振能量转移和Trp-Cys猝灭探测到的不同距离范围，得到了与实验符合良好的定量的扩散估计。
Intramolecular protein diffusion, the motion of one part of the polypeptide chain relative to another part, is a fundamental aspect of protein folding and may modulate amyloidogenesis of disease-associated intrinsically disordered proteins. Much work has determined such diffusion coefficients using a variety of probes, but there has been an apparent discrepancy between measurements using long-range probes, such as fluorescence resonance energy transfer, and short-range probes, such as Trp-Cys quenching. In this work, we make both such measurements on the same protein,α-synuclein, and confirm that such discrepancy exists. Molecular dynamics simulations suggest that such differences result from a diffusion coefficient that depends on the spatial distance between probes. Diffusional estimates in good quantitative agreement with experiment are obtained by accounting for the distinct distance ranges probed by fluorescence resonance energy transfer and Trp-Cys quenching.