Effect of glucocorticoids and their complexes with apolipoprotein A-I on the secondary structure of eukaryotic DNA

摘要

The tetrahydrocortisol-apohpoprotein A-I complex specifically interacts with eukaryotic DNA isolated from rat liver. This interaction is highly cooperative and of a saturating nature. One DNA molecule binds about 54 molecules of the complex. Small-angle X-ray scattering has shown that hydrogen bonds between nitrous bases are destroyed and that single-stranded structures are formed at the interaction of the tetrahydrocortisol-apolipoprotein A-I complex with eukaryotic DNA. The most probable site of binding the tetrahydrocortisol-apolipoprotein A-I complex with DNA is the sequence of the CC(GCC)(n) type entering the structure of many genes, among them the structure of the human apolipoprotein A-I gene. Oligonucleotide of this type has been synthesized. The association constant (K-ass) of its complexation was shown to be 1.66 (.) 10(6) M-1. Substitution of tetrahydrocortisol for cortisol in the complex results in a considerable decrease of K-ass. IR-spectroscopy study has shown that the interaction of tetrahydrocortisol with oligonucleotide CC(GCC)(3-5) is accompanied by the formation of hydrogen bonds via the CO-NH, PO2, and OH groups of desoxycytidinephosphate. The tetrahydrocortisol-apolipoprotein A-I complex alters the DNA secondary structure formed at the interaction with the hormone, causing the structural transition "order --> tangle." It is assumed that in the GC-pairs of the given DNA sequence, tetrahydrocortisol initiates the rupture of hydrogen bonds, while the hydrophobic interactions between nitrous bases and apoA-I intensify this process. (C) 2004 Wiley Periodicals, Inc.