Protein: Feeling the Groove of DNA

Watkins, Davita L.; Harris, Lydia-Ann; Koudelka, Gerald B.; Williams, Loren Dean

doi:10.1021/bk-2011-1082.ch008

Cited by 3 publications

(4 citation statements)

References 45 publications

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“…We previously suggested that a key determinant for non-contacted base recognition, and thus binding site discrimination by P22R, is the propensity of various base sequences to assume the B′-DNA state ( 9 – 10 , 17 ). This B→B′ transition is characterized by substantial narrowing of the minor groove from 12 Å→2.2 Å and formation of a highly organized stacked monolayer of rotationally and translationally restrained water molecules ( 8 – 10 ). Here we show that a P22R binding site containing a ‘pre-formed’, B′-like solvent network in the minor groove strongly binds P22R.…”

Section: Discussionmentioning

confidence: 99%

“…The sequences of the contacted bases in each of the six naturally occurring P22R DNA binding sites are nearly identical (Figure 1A ). X-ray structural analyses show that no protein atoms closely approach any of the major or minor groove functional groups on the bases at the center of the P22R binding site ( 8 – 10 ), meaning that P22R discriminates between these similar sequence binding sites by indirectly reading the sequence of non-contacted bases at the center of the P22R binding site.…”

Section: Introductionmentioning

confidence: 99%

“…P22R binding induces a B → B′ transition in the non-contacted region of the binding site, irrespective of the non-contacted base sequence and base identity ( 9 , 10 ). However, the minor groove solvation pattern in the induced B′ region varies with its sequence.…”

Section: Introductionmentioning

confidence: 99%

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Specific minor groove solvation is a crucial determinant of DNA binding site recognition

Harris¹,

Williams²,

Koudelka³

2014

Nucleic Acids Research

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The DNA sequence preferences of nearly all sequence specific DNA binding proteins are influenced by the identities of bases that are not directly contacted by protein. Discrimination between non-contacted base sequences is commonly based on the differential abilities of DNA sequences to allow narrowing of the DNA minor groove. However, the factors that govern the propensity of minor groove narrowing are not completely understood. Here we show that the differential abilities of various DNA sequences to support formation of a highly ordered and stable minor groove solvation network are a key determinant of non-contacted base recognition by a sequence-specific binding protein. In addition, disrupting the solvent network in the non-contacted region of the binding site alters the protein's ability to recognize contacted base sequences at positions 5–6 bases away. This observation suggests that DNA solvent interactions link contacted and non-contacted base recognition by the protein.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Specific minor groove solvation is a crucial determinant of DNA binding site recognition

Harris¹,

Williams²,

Koudelka³

2014

Nucleic Acids Research

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“…Further studies have shown that monovalent cation binding to the A-tract minor groove likely occurs at most one-third of the time [ 56 , 57 ], and that excess monovalent cation binding to the A-tract minor groove is not the cause of the unique A-tract conformation [ 20 ]. These latter studies propose that monovalent cations may be linked to a conformation transition (from B-DNA to so-called B*-DNA or B′-DNA) with the formation of a narrow minor groove, and that specific protein contacts can drive generic DNA sequences into this conformation [ 58 , 59 ].…”

Section: Introductionmentioning

confidence: 99%

Examining the Effects of Netropsin on the Curvature of DNA A-Tracts Using Electrophoresis

Miller

Peters

2021

Molecules

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A-tracts are sequences of repeated adenine bases that, under the proper conditions, are capable of mediating DNA curvature. A-tracts occur naturally in the regulatory regions of many organisms, yet their biological functions are not fully understood. Orienting multiple A-tracts together constructively or destructively in a phase has the potential to create different shapes in the DNA helix axis. One means of detecting these molecular shape differences is from altered DNA mobilities measured using electrophoresis. The small molecule netropsin binds the minor groove of DNA, particularly at AT-rich sequences including A-tracts. Here, we systematically test the hypothesis that netropsin binding eliminates the curvature of A-tracts by measuring the electrophoretic mobilities of seven 98-base pair DNA samples containing different numbers and arrangements of centrally located A-tracts under varying conditions with netropsin. We find that netropsin binding eliminates the mobility difference between the DNA fragments with different A-tract arrangements in a concentration-dependent manner. This work provides evidence for the straightening of A-tracts upon netropsin binding and illustrates an artificial approach to re-sculpt DNA shape.

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Indirect Readout of DNA Sequence by P22 Repressor: Roles of DNA and Protein Functional Groups in Modulating DNA Conformation

Harris

Watkins

Williams

et al. 2013

Journal of Molecular Biology

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Protein: Feeling the Groove of DNA

Cited by 3 publications

References 45 publications

Specific minor groove solvation is a crucial determinant of DNA binding site recognition

Specific minor groove solvation is a crucial determinant of DNA binding site recognition

Examining the Effects of Netropsin on the Curvature of DNA A-Tracts Using Electrophoresis

Indirect Readout of DNA Sequence by P22 Repressor: Roles of DNA and Protein Functional Groups in Modulating DNA Conformation

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