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Control of DNA minor groove width and Fis protein binding by the purine 2-amino group

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkt357· OSTI ID:1091101
 [1];  [2];  [1];  [3];  [3];  [1]
  1. University of California, Los Angeles, CA (United States)
  2. CNR Institute of Nanoscience, Modena (Italy)
  3. University of Southern California, Los Angeles, CA (United States)
The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis–DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis–DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Alfred P. Sloan Research Fellowship; Italian Institute of Technology; National Institutes of General Medical Sciences; National Institutes of Health (NIH); USDOE
Grant/Contract Number:
AC02-06CH11357; FC02-02ER63421
OSTI ID:
1091101
Alternate ID(s):
OSTI ID: 1088537
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 13 Vol. 41; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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Flanking A·T Basepairs Destabilize the B∗ Conformation of DNA A-Tracts journal May 2015
Absence of a simple code: how transcription factors read the genome journal September 2014
HÆMatology journal March 1969
Elasticity as the Basis of Allostery in DNA journal December 2018
The Unusual Monomer Recognition of Guanine-Containing Mixed Sequence DNA by a Dithiophene Heterocyclic Diamidine journal February 2014
DNA Methylation Reduces Binding and Cleavage by Bleomycin journal September 2014
Design and Synthesis of Heterocyclic Cations for Specific DNA Recognition: From AT-Rich to Mixed-Base-Pair DNA Sequences journal January 2014
Structure-function analysis of the DNA-binding domain of a transmembrane transcriptional activator journal April 2017
New protein-DNA complexes in archaea: a small monomeric protein induces a sharp V-turn DNA structure journal October 2019
TFBSshape: a motif database for DNA shape features of transcription factor binding sites journal November 2013
Specific minor groove solvation is a crucial determinant of DNA binding site recognition journal November 2014
Heterogeneity of Transcription Factor binding specificity models within and across cell lines posted_content October 2015
A machine learning approach for predicting CRISPR-Cas9 cleavage efficiencies and patterns underlying its mechanism of action journal October 2017
DNA Sequence Determinants Controlling Affinity, Stability and Shape of DNA Complexes Bound by the Nucleoid Protein Fis journal March 2016
A unified approach for quantifying and interpreting DNA shape readout by transcription factors journal February 2018
Energy Transfer as A Driving Force in Nucleic Acid–Protein Interactions journal April 2019
Allosteric interactions in a birod model of DNA text January 2018

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