Searching DNA via a "Monkey Bar" Mechanism: The Significance of Disordered Tails
Searching DNA via a "Monkey Bar" Mechanism: The Significance of Disordered Tails
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DOI：
10.1016/j.jmb.2009.11.056
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发表时间：
2010-02-26
影响因子：
5.6
通讯作者：
Levy, Yaakov
中科院分区：
文献类型：
--
作者：
Vuzman, Dana;Azia, Ariel;Levy, Yaakov
蛋白质对特定位点的非特异性DNA搜索是通过在不同的DNA链之间滑动、跳跃和片段间转移来实现的，但从分子角度来看，这些蛋白质动力学的驱动力尚不清楚。在这项研究中，利用一个简单的计算模型探索了三种同源蛋白质(HoxD9、ANTP和NK-2同源结构域)的DNA搜索机制的分子特征，在该模型中，蛋白质-DNA相互作用仅由静电力表示。特别是，我们研究了在DNA结合蛋白中比在其他蛋白质中更常见的无序N末端尾巴(N-Tail)对DNA搜索效率的影响。虽然这三种同源结构域蛋白在与DNA的特定和非特异性相互作用中使用相似的结合界面，但它们不同的静电势影响其滑动动力学的性质。同源结构域N-尾部的不同长度和净电荷会影响它们沿DNA的运动。N-尾的存在增加了滑动倾向，但减缓了沿DNA的线性扩散。当在两个平行的DNA分子存在的情况下进行搜索时，就会发生由蛋白质尾巴促进的从一个非特异性DNA到另一个的直接转移。拖尾的蛋白质通过一个中间体在两个DNA分子之间跳跃，在这个中间体中，蛋白质的识别螺旋被吸附到一个DNA片段上，N-尾巴吸附到第二个DNA片段上，这表明这是一种“猴子棒”机制。我们的研究说明了蛋白质的分子结构如何控制DNA扫描的效率。(C)2009爱思唯尔有限公司。保留所有权利。
The search through nonspecific DNA for a specific site by proteins is known to be facilitated by sliding, hopping, and intersegment transfer between separate DNA strands, yet the driving forces of these protein dynamics from the molecular perspective are unclear. In this study, molecular features of the DNA search mechanism were explored for three homologous proteins (the HoxD9, Antp, and NK-2 homeodomains) using a simple computational model in which protein-DNA interactions are represented solely by electrostatic forces. In particular, we studied the impact that disordered N-terminal tails (N-tails), which are more common in DNA-binding proteins than in other proteins, have on the efficiency of DNA search. While the three homeodomain proteins were found to use similar binding interfaces in specific and nonspecific interactions with DNAs, their different electrostatic potentials affect the nature of their sliding dynamics. The different lengths and net charges of the N-tails of the homeodomains affect their motion along the DNA. The presence of an N-tail increases sliding propensity but slows linear diffusion along the DNA. When the search is performed in the presence of two parallel DNA molecules, a direct transfer, which is facilitated by the protein tail, from one nonspecific DNA to another occurs. The tailed proteins jump between two DNA molecules through an intermediate in which the recognition helix of the protein is adsorbed to one DNA fragment and the N-tail is adsorbed to the second, suggesting a "monkey bar" mechanism. Our study illustrates how the molecular architecture of proteins controls the efficiency of DNA scanning. (C) 2009 Elsevier Ltd. All rights reserved.