Poly(dA-dT) has a right-handed B conformation in solution: a two-dimensional NMR study

Area of Science:

• Molecular Biology
• Biophysics
• Structural Biology

Background:

• Poly(dA-dT) is a synthetic DNA polymer with a simple repeating sequence.
• Understanding DNA structure in solution is crucial for molecular biology.
• Previous models proposed distinct sugar puckers for adenine and thymine nucleotides.

Purpose of the Study:

• To elucidate the solution structure of poly(dA-dT) molecules.
• To investigate internucleotide and intranucleotide interactions within poly(dA-dT).
• To determine the conformation of adenine and thymine nucleotides.

Main Methods:

• Two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY).
• Analysis of cross-relaxation patterns from proton-proton interactions.
• Assignment of sugar proton resonances.

Main Results:

• Poly(dA-dT) adopts a right-handed helical structure with a B-type conformation.
• Both adenine and thymine nucleotides exist in an anti conformation.
• Observed interactions did not support significant differences in sugar pucker between adenine and thymine nucleotides as suggested by prior models.
• Unexpected cross-strand AH2-AH2 interactions were observed at low temperatures.

Conclusions:

• The solution structure of poly(dA-dT) is a right-handed B-form helix.
• Nucleotide conformations are consistent with typical B-DNA.
• The study refutes models suggesting large differences in sugar pucker between adenine and thymine in this context.
• Low-temperature data suggest novel inter-strand interactions in poly(dA-dT).