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.
Rohs
Remo
R
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.
West
Sean M
SM
Sosinsky
Alona
A
Liu
Peng
P
Mann
Richard S
RS
Honig
Barry
B
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