Control of DNA minor groove width and Fis protein binding by the purine 2-amino group
- University of California, Los Angeles, CA (United States)
- CNR Institute of Nanoscience, Modena (Italy)
- 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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