Article

The role of DNA shape in protein-DNA recognition

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.
Nature (Impact Factor: 42.35). 10/2009; 461(7268):1248-53. DOI: 10.1038/nature08473
Source: PubMed

ABSTRACT 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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    • "Remarkably, the CXC domain uses a single arginine to directly read out dinucleotide sequences from the minor groove of DNA, distinct from other DNA-binding domains that commonly recognize DNA sequence from the major groove with large secondary structure elements (Freemont et al. 1991). Arginine has been documented to interact with the minor groove but, in most cases, indirectly reads out DNA sequences by binding narrow minor grooves adopted by AT-rich sequences (Rohs et al. 2009). A single small CXC domain offers only limited binding specificity and affinity. "
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