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[交流] Nature：DNA结合蛋白如何识别特异性DNA序列

Nature：DNA结合蛋白如何识别特异性DNA序列

序列特异性DNA结合蛋白何以能在数量巨大的非特异性DNA中找到目标是一个长期未解之谜。一个比较受欢迎的模型是，序列是作为DNA螺旋的“大沟”中蛋白与碱基之间氢键的形成被读取的。对蛋白-DNA复合物三维结构所做的一项新的分析表明，DNA形状是识别的关键。DNA序列的前后部分通过让精氨酸优先与带负电的“口袋”结合改变DNA螺旋“小沟”的宽度。DNA在核小体核心颗粒中的定位是这一效应的一个例子。

Nature 461, 1248-1253 (29 October 2009) | doi:10.1038/nature08473

The role of DNA shape in protein–DNA recognition

Remo Rohs1,3, Sean M. West1,3, Alona Sosinsky1,4, Peng Liu1, Richard S. Mann2 & Barry Honig1

1 Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biophysics, Columbia University, 1130 Saint Nicholas Avenue, New York, New York 10032, USA
2 Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, HHSC 1104, New York, New York 10032, USA
3 These authors contributed equally to this work.
4 Present address: Institute of Structural and Molecular Biology, School of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK.
5 Correspondence to: Richard S. Mann2Barry Honig1 Correspondence and requests for materials should be addressed to B.H. or R.S.M.

The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. By comprehensively analysing the three-dimensional structures of protein–DNA complexes, here we show that the binding of arginine residues to narrow minor grooves is a widely used mode for protein–DNA recognition. This readout mechanism exploits the phenomenon that narrow minor grooves strongly enhance the negative electrostatic potential of the DNA. The nucleosome core particle offers a prominent example of this effect. Minor-groove narrowing is often associated with the presence of A-tracts, AT-rich sequences that exclude the flexible TpA step. These findings indicate that the ability to detect local variations in DNA shape and electrostatic potential is a general mechanism that enables proteins to use information in the minor groove, which otherwise offers few opportunities for the formation of base-specific hydrogen bonds, to achieve DNA-binding specificity.

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