Fly-casting in protein-DNA binding: Frustration between protein folding and electrostatics facilitates target recognition
Fly-casting in protein-DNA binding: Frustration between protein folding and electrostatics facilitates target recognition
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DOI：
10.1021/ja065531n
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发表时间：
2007-01-31
影响因子：
15
通讯作者：
Wolynes, Peter G.
中科院分区：
文献类型：
--
作者：
Levy, Yaakov;Onuchic, Jose N.;Wolynes, Peter G.
分子可塑性是许多生物分子自组装过程的关键，而静电导向则是将蛋白质引导到DNA，这两者被证明是耦合的，并促进了DNA的搜索。虽然蛋白质的灵活性与诱导配合识别有关，并且在更大程度上与本质上非结构化的DNA结合蛋白有关，但我们表明，通过“潮汐力”，DNA的静电场可以诱导灵活性和双态折叠蛋白的部分展开，从而降低其折叠屏障，从而刺激飞铸。该蛋白以非特异性的部分折叠状态结合DNA，并在结合特定位点时完成折叠。即使对于弱静电力，也可以观察到飞铸和静电之间的相互作用，并且由于盐和固有折叠屏障的静电屏蔽而变化，这两者都可以通过实验调节。
Molecular plasticity, the key to many biomolecular self-assembly processes, and electrostatic steering, which guides proteins to DNA, are shown to be coupled and to facilitate DNA search. While protein flexibility is involved in induced-fit recognition and to a larger extent in intrinsically unstructured DNA binding proteins, we show that through a "tidal force" the electrostatic field of the DNA can induce flexibility and the partial unfolding of a two-state folding protein, thereby reducing its folding barrier and, thus, stimulating fly-casting. The protein binds DNA nonspecifically in a partially folded state and completes its folding when it binds the specific site. The interplay between fly-casting and electrostatics is observed even for weak electrostatic forces and is expected to vary with the electrostatic screening due to salt and the intrinsic folding barrier, both of which can be modulated experimentally.