The role of DNA shape in protein–DNA recognition

Abstract

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.

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

“…These very low stringency requirements for binding site matches make LeuO a useful antagonist for the transcription silencer, H-NS, with its preference for binding to A + T-rich DNA (Dillon et al 2012). A predilection for A + T-rich DNA means that proteins like LeuO and other winged helix-turn-helix proteins must dock with DNA, where the minor groove is up to three times narrower than in more G + C-rich sequences (Oguey et al 2010;Rohs et al 2009). Supercoiling such DNA sequences to different levels is itself likely to impose restrictions on successful DNA binding.…”

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

“…However, many details of the mechanisms of the protein search for targets on DNA still remain not well understood. [27][28][29][30][31] One of the most fascinating observations in this field is that many proteins can find and recognize their specific binding sites much faster than expected if the search would take place only via 3D bulk diffusion. 3,5,6,27,28 This surprising result is called a facilitated diffusion, and it is frequently argued that this happens due to the protein search being a combination of 3D and 1D modes.…”

The Fur homologue BosR requires Arg39 to activate rpoS transcription in Borrelia burgdorferi and thereby direct spirochaete infection in mice

“…However, arginine differs from lysine in that it more readily inserts itself into narrowed minor grooves and can therefore be used for protein-DNA recognition (Rohs et al, 2009). Narrow minor grooves exist in A-tract DNA.…”