Long-Range Correlated Dynamics in Intrinsically Disordered Proteins
Long-Range Correlated Dynamics in Intrinsically Disordered Proteins
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DOI：
10.1021/ja506820r
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发表时间：
2014-11-19
影响因子：
15
通讯作者：
Luchinat, Claudio
中科院分区：
文献类型：
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作者：
Parigi, Giacomo;Rezaei-Ghaleh, Nasrollah;Luchinat, Claudio
本质无序蛋白 (IDP) 参与多种生理和病理过程，最好通过快速相互转换的构象异构体来描述。使用快速场循环松弛测量，我们在此表明，IDP α-突触核蛋白以及各种其他 IDP 在与折叠蛋白质相当的时间尺度上经历缓慢的重新定向。慢动作不受α-突触核蛋白突变的干扰，α-突触核蛋白突变与帕金森病的遗传形式有关，并且不依赖于二级和三级结构倾向。基于系综的流体动力学计算表明，潜在相关运动的时间尺度很大程度上是由局部刚性段之间的流体动力学耦合决定的。我们的研究表明，长程相关动力学是 IDP 的固有属性，并提供了高度灵活的生物分子系统中相关运动的一般物理机制。
Intrinsically disordered proteins (IDPs) are involved in a wide variety of physiological and pathological processes and are best described by ensembles of rapidly interconverting conformers. Using fast field cycling relaxation measurements we here show that the IDP alpha-synuclein as well as a variety of other IDPs undergoes slow reorientations at time scales comparable to folded proteins. The slow motions are not perturbed by mutations in alpha-synuclein, which are related to genetic forms of Parkinson's disease, and do not depend on secondary and tertiary structural propensities. Ensemble-based hydrodynamic calculations suggest that the time scale of the underlying correlated motion is largely determined by hydrodynamic coupling between locally rigid segments. Our study indicates that long-range correlated dynamics are an intrinsic property of IDPs and offers a general physical mechanism of correlated motions in highly flexible biomolecular systems.