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DNA 中协同双态平衡的定量模型:实验测试、见解和预测。

A quantitative model of a cooperative two-state equilibrium in DNA: experimental tests, insights, and predictions.

机构信息

Department of Chemistry, University of Washington, Box 351700, Seattle, WA98195-1700, USA.

出版信息

Q Rev Biophys. 2021 Mar 16;54:e5. doi: 10.1017/S0033583521000032.

DOI:10.1017/S0033583521000032
PMID:33722316
Abstract

Quantitative parameters for a two-state cooperative transition in duplex DNAs were finally obtained during the last 5 years. After a brief discussion of observations pertaining to the existence of the two-state equilibrium per se, the lengths, torsion, and bending elastic constants of the two states involved and the cooperativity parameter of the model are simply stated. Experimental tests of model predictions for the responses of DNA to small applied stretching, twisting, and bending stresses, and changes in temperature, ionic conditions, and sequence are described. The mechanism and significance of the large cooperativity, which enables significant DNA responses to such small perturbations, are also noted. The capacity of the model to resolve a number of long-standing and sometimes interconnected puzzles in the extant literature, including the origin of the broad pre-melting transition studied by numerous workers in the 1960s and 1970s, is demonstrated. Under certain conditions, the model predicts significant long-range attractive or repulsive interactions between hypothetical proteins with strong preferences for one or the other state that are bound to well-separated sites on the same DNA. A scenario is proposed for the activation of the ilvPG promoter on a supercoiled DNA by integration host factor.

摘要

在过去的 5 年中,终于获得了双链 DNA 中两态协同转变的定量参数。简要讨论了关于两态平衡本身存在的观察结果后,简单说明了所涉及的两种状态的长度、扭转和弯曲弹性常数以及模型的协同参数。描述了对 DNA 对小拉伸、扭转和弯曲应力以及温度、离子条件和序列变化的响应的模型预测的实验测试。还注意到了大协同作用的机制和意义,这种大协同作用使 DNA 对如此小的干扰产生显著反应成为可能。该模型能够解决现存文献中许多长期存在且有时相互关联的难题,包括 20 世纪 60 年代和 70 年代许多研究人员研究的广泛预熔转变的起源。在某些条件下,该模型预测了具有强烈偏好一种状态的假设蛋白质之间在同一 DNA 上的相隔较远的位点之间存在显著的长程吸引或排斥相互作用。提出了整合宿主因子激活超螺旋 DNA 上的 ilvPG 启动子的方案。

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Q Rev Biophys. 2021 Mar 16;54:e5. doi: 10.1017/S0033583521000032.
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