Mendel-Brno 2000

category image Volume: 17
Issue Number 6, Part 2
June 2000

DNA Bending, Sugar Puckering and Protein-DNA Interactions

Using high frequency antiphase NMR spectroscopy and computer simulations of the antiphase spectra, we studied the equilibria in the sugar conformations in the DNA duplex 11-mer containing the AAA tract surrounded by cytosines. We demonstrate that at the 3'-end of the A-tract, the sugar switches from the common S-conformer (B-like form) to the N-conformer (A-like form) with the probability of 50-60%, thus creating a purine-pyrimidine step with heteronomous characteristics. The presence of this local B-A junction in one strand leads to compression of the interphosphate distance in this strand. We calculate the effect of this sugar switch on the helical parameters that are related to DNA bending.

Based on these data, we suggest that in AnC stretches, DNA bending is a complicated dynamic process, i.e., locally noncanonical N conformers of the sugar-phosphate backbone mix in with the B-like S conformers leading to global bending. We present detailed structures comprising the ensemble of bent DNA's and provide arguments that the sugar conformation at the 3'-end of the A-tract may serve as a recognition element for DNA binding proteins.

In particular, we found that this local sugar switch exposes the hydrophobic groups in the minor groove by analogy with the B-to-A transition. These groups are recognized by phenylalanines and other hydrophobic amino acids (e.g., in TBP proteins interacting with TATA-boxes through the minor groove). Thus, the local B-to-A-like transformation and interaction with proteins can be better understood based on comparisons with the DNA surface accessibility calculations.

Shantaram Kamath1, Mukti H. Sarma1, Michael Tosltorukov2, Victor Zhurkin2, Chris Turner3, and Ramaswamy H. Sarma1.

1Institute of Biomolecular Stereodynamics, Chemisty
SUNY at Albany, Albany NY 12222
2Molecular Structure Section, Laboratory of Computational and Experimental Biology,
National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892-5677
3Francis Bitter Magnet Laboratory,
Massachusetts Institute of Technology,
170 Albany Street, Cambridge, MA 02139