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The recognition of specific DNA sequences by proteins is thought to depend on two types of...

The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanisms: 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 analyzing the three-dimensional structures of protein-DNA complexes, we show that the binding of arginines 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 striking 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 suggest 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

1. What three properties of the major groove are advantageous to alpha helix insertion?

2. Which nucleotides are prevalent in narrow minor grooves?

3. Which amino acid tends to bind to the minor groove and how are minor groove width and electrostatic potential correlated?

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Answer #1

1. What three properties of the major groove are advantageous to alpha helix insertion?

Answer: 1) formation of hydrogen bonds with specific bases

2) sequence-dependent deformations of the DNA helix

3) Groove width is wider as compared to minor groove

2. Which nucleotides are prevalent in narrow minor grooves?

Answer: AT rich sequences are present in narrow minor grooves. 78% of being an AT and 22% of being a GC. AT rich sequences in minor grooves offer binding site for arginine residues of DNA binding proteins.

3. Which amino acid tends to bind to the minor groove and how are minor groove width and electrostatic potential correlated?

Answer: Arginine amino acid tends to bind the minor groove and constitutes 28% of all amino acid that binds to minor groove of DNA.

Narrow minor grooves (a groove width of <5.0 Å as compared to 5.8 Å in ideal B-DNA) strongly enhance the negative electrostatic potential of the DNA.This correlation is mainly due to the properties of the Poisson-Boltzmann (PB) equation.

Reference: Rohs, Remo, et al. "The role of DNA shape in protein–DNA recognition." Nature 461.7268 (2009): 1248.

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