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利用磁镊探究核酸的力学性质、构象变化及相互作用。

Probing the mechanical properties, conformational changes, and interactions of nucleic acids with magnetic tweezers.

作者信息

Kriegel Franziska, Ermann Niklas, Lipfert Jan

机构信息

Department of Physics, Nanosystems Initiative Munich, and Center for Nanoscience, LMU Munich, Amalienstr. 54, 80799 Munich, Germany.

Department of Physics, Nanosystems Initiative Munich, and Center for Nanoscience, LMU Munich, Amalienstr. 54, 80799 Munich, Germany.

出版信息

J Struct Biol. 2017 Jan;197(1):26-36. doi: 10.1016/j.jsb.2016.06.022. Epub 2016 Jun 29.

Abstract

Nucleic acids are central to the storage and transmission of genetic information. Mechanical properties, along with their sequence, both enable and fundamentally constrain the biological functions of DNA and RNA. For small deformations from the equilibrium conformations, nucleic acids are well described by an isotropic elastic rod model. However, external forces and torsional strains can induce conformational changes, giving rise to a complex force-torque phase diagram. This review focuses on magnetic tweezers as a powerful tool to precisely determine both the elastic parameters and conformational transitions of nucleic acids under external forces and torques at the single-molecule level. We review several variations of magnetic tweezers, in particular conventional magnetic tweezers, freely orbiting magnetic tweezers and magnetic torque tweezers, and discuss their characteristic capabilities. We then describe the elastic rod model for DNA and RNA and discuss conformational changes induced by mechanical stress. The focus lies on the responses to torque and twist, which are crucial in the mechanics and interactions of nucleic acids and can directly be measured using magnetic tweezers. We conclude by highlighting several recent studies of nucleic acid-protein and nucleic acid-small-molecule interactions as further applications of magnetic tweezers and give an outlook of some exciting developments to come.

摘要

核酸对于遗传信息的存储和传递至关重要。机械特性及其序列,既赋予了DNA和RNA生物学功能,又从根本上对其进行了限制。对于偏离平衡构象的小变形,核酸可用各向同性弹性杆模型很好地描述。然而,外力和扭转应变会引发构象变化,从而产生复杂的力-扭矩相图。本综述重点介绍磁镊这一强大工具,它能在单分子水平上精确测定核酸在外部力和扭矩作用下的弹性参数和构象转变。我们回顾了磁镊的几种变体,特别是传统磁镊、自由轨道磁镊和磁扭矩镊,并讨论了它们的独特能力。然后我们描述了DNA和RNA的弹性杆模型,并讨论了机械应力引起的构象变化。重点在于对扭矩和扭转的响应,这在核酸的力学和相互作用中至关重要,并且可以使用磁镊直接测量。我们最后强调了核酸-蛋白质和核酸-小分子相互作用的几项最新研究,作为磁镊的进一步应用,并展望了未来一些令人兴奋的发展。

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