The role of DNA shape in protein-DNA recognition.
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.
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.
Remo
R
Rohs
Sean M
SM
West
Alona
A
Sosinsky
Peng
P
Liu
Richard S
RS
Mann
Barry
B
Honig
D020856:AT Rich Sequence / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016208:Databases, Factual; D006860:Hydrogen Bonding; D008239:Lysine; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae; D055672:Static Electricity
D004268:DNA-Binding Proteins; D009707:Nucleosomes; D004247:DNA; D001120:Arginine; D008239:Lysine