Multiple four-stranded conformations of human telomere sequence d(CCCTAA) in solution.
By detailed NMR analysis of a human telomere repeating unit, d(CCCTAA), we have found that three distinct tetramers, each of which consists of four symmetric single-strands, slowly exchange in a slightly acidic solution. Our new finding is a novel i-motif topology (T:-form) where T4 is intercalated between C1 and C2 of the other duplex. The other two tetramers have a topology where C1 is intercalated between C2 and C3 of the other parallel duplex, resulting in the non-stacking T4 residues (R-form), and a topology where C1 is stacked between C3 and T4 of the other duplex (S:-form). From the NMR denaturation profile, the R-form is the most stable of the three structures in the temperature range of 15-50 degrees C, the S:-form the second and the T:-form the least stable. The thermodynamic parameters indicate that the T-form is the most enthalpically driven and entropically opposed, and its population is increased with decreasing temperature. The T-form structure determined by restrained molecular dynamics calculation suggests that inter-strand van der Waals contacts in the narrow grooves should contribute to the enthalpic stabilization of the T-form.
Kanaori
K
K
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. kanaori@ipc.kit.ac.jp
Shibayama
N
N
Gohda
K
K
Tajima
K
K
Makino
K
K
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D013696:Temperature; D013816:Thermodynamics
D009841:Oligonucleotides; D004247:DNA