Structural Basis for DNA Bending

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 8; pp. 2622 - 2626
• Main Authors: Nadeau, James G., Crothers, Donald M.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-04-1989; National Acad Sciences
• Subjects: 550601 - Medicine- Unsealed Radionuclides in Diagnostics; Analytical, structural and metabolic biochemistry; BARYONS; Bending; Biochemistry; Biological and medical sciences; Chemical equilibrium; CHEMICAL SHIFT; CHROMATOGRAPHY; CONFORMATIONAL CHANGES; Conformity; Crystal structure; CRYSTALLOGRAPHY; DNA; DNA - ultrastructure; Dna, deoxyribonucleoproteins; ELEMENTARY PARTICLES; FERMIONS; Fundamental and applied biological sciences. Psychology; HADRONS; ION EXCHANGE CHROMATOGRAPHY; MAGNETIC RESONANCE; Magnetic Resonance Spectroscopy; NMR SPECTRA; NUCLEAR MAGNETIC RESONANCE; Nucleic Acid Conformation; NUCLEIC ACIDS; NUCLEONS; Oligodeoxyribonucleotides; OLIGONUCLEOTIDES; ORGANIC COMPOUNDS; OVERHAUSER EFFECT; Propellers; PROTONS; RADIOLOGY AND NUCLEAR MEDICINE; RESONANCE; SEPARATION PROCESSES; SPECTRA; STRUCTURAL MODELS; Molecular bending; Oligonucleotide; NMR spectrometry
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.8.2622

We report proton NMR studies on DNA oligonucleotides that contain A tracts of lengths known to produce various degrees of bending. Spectra of duplexes in the series 5′-(GGCAnCGG)· (CCGTnGCC) (n = 3,4,5,7,9) reveal substantial structural changes within the An· Tntract as its length is increased. Chemical-shift comparisons show that A tracts with fewer than about seven members do not contain regions of uniform [or poly(dA)· poly(dT)-like] structure. Long Antracts (n ≥ 7) appear to consist of an internal segment of homopolymeric conformation flanked by regions of transitional structure that occupy about four A· T pairs on the 5′side and two A· T pairs and perhaps the directly adjacent G· C pair on the 3′side. In shorter duplexes (n < 7), these two transitional regions overlap and an apparent mutual incompatibility causes length-dependent changes that are most pronounced near the 3′end. Throughout the series, there is a striking monotonic relationship between the location of an A· T pair in the A tract and the relative position of its ThyH3 resonance. The direction of this chemical-shift dispersion is opposite to that expected from consideration of ring-current effects alone; this discrepancy suggests a gradual decrease in ThyH3⋯ N1Ade hydrogen-bond length as one moves from the 5′to the 3′end of the A tract and from short to long A tracts. Nuclear Overhauser effect measurements reveal that the interproton distances AdeH2⋯ H1′Ade and AdeH2⋯ H1′Thy vary along each A tract, except in the central regions of the longer ones where they are fairly constant and in good agreement with the poly(dA)· poly(dT) structure proposed by Lipanov, A. A. & Chuprina, V. P. [(1987) Nucleic Acids Res. 15, 5833-5844]. This model features a substantial negative base-pair tilt, which has been suggested previously as the source of A-tract bending. In contrast, the nuclear Overhauser effect distances are inconsistent with at least one known crystallographic A-tract structure [DiGabriele, A. D., Sanderson, M. R. & Steitz, T. A. (1989) Proc. Natl. Acad. Sci. USA 86, 1816-1820], which lacks appreciable base-pair tilt.