序列特異性DNA結(jié)合蛋白何以能在數(shù)量巨大的非特異性DNA中找到目標(biāo)是一個(gè)長(zhǎng)期未解之謎,。一個(gè)比較受歡迎的模型是,，序列是作為DNA螺旋的“大溝”中蛋白與堿基之間氫鍵的形成被讀取的。對(duì)蛋白-DNA復(fù)合物三維結(jié)構(gòu)所做的一項(xiàng)新的分析表明,，DNA形狀是識(shí)別的關(guān)鍵。DNA序列的前后部分通過(guò)讓精氨酸優(yōu)先與帶負(fù)電的“口袋”結(jié)合改變DNA螺旋“小溝”的寬度。DNA在核小體核心顆粒中的定位是這一效應(yīng)的一個(gè)例子,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
