Changes in the secondary structure of highly polymeric DNA and CC(GCC)n-type oligonucleotides under the action of steroid hormones and their complexes with apolipoprotein A I.
A small-angle X-ray scattering study showed that the action of tetrahydrocortisol (THC) in complex with apolipoprotein A I (ApoA-I) on DNA leads to local melting of DNA. The most probable site of interaction between this complex and DNA is the (GCC)n-type sequence. Oligonucleotides (duplexes) of this type have been synthesized. It was demonstrated that the interaction of this oligonucleotide with the THC-ApoA-I complex leads to dissociation into complementary oligonucleotides. The latter ones also interact with the THC-ApoA-I complex. The kinetics of this multistep process is presented. The mechanism of interaction between hormones or their ApoA-I complexes and duplex CC(GCC)5.GG(CGG)5Li2 was studied using IR spectroscopy. It was shown that the interaction with THC or the THC-ApoA-I complex leads to the formation of hydrogen bonds between the OH group of the hormone A-ring and the C=O group of cytosine or guanine. Interaction with cortisol or the cortisol-ApoA-I complex leads to the formation of a hydrogen bond with the NH group of cytosine; in addition, THC and cortisol form hydrogen bonds with the PO2 group of the duplex and with the OH group of the monosaccharide. The interaction of ApoA-I with the duplex is accompanied by the formation of hydrogen bonds between the protein NH2 group and the C=O group of cytosine and the P=O group. The order-to-order structural transition takes place in the duplex under the action of THC or cortisol, with THC causing a higher ordering as compared to cortisol. The order-to-disorder structural transition occurs in the duplex under the action of the THC-ApoA-I, cortisol-ApoA-I, or ApoA-I complexes. Shifting the pH of the medium from 7.2 to 6.0 also leads to an order-to-disorder-type structural transition.