Format

Send to

Choose Destination
See comment in PubMed Commons below
Nucleic Acids Res. 2013 Jul;41(13):6750-60. doi: 10.1093/nar/gkt357. Epub 2013 May 9.

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

Author information

1
Department of Biological Chemistry, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095-1737, USA.

Abstract

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.

PMID:
23661683
PMCID:
PMC3711457
DOI:
10.1093/nar/gkt357
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center