Origin of overstretching transitions in single-stranded nucleic acids.
We combined single-molecule force spectroscopy with nuclear magnetic resonance measurements and molecular mechanics simulations to examine overstretching transitions in single-stranded nucleic acids. In single-stranded DNA and single-stranded RNA there is a low-force transition that involves unwinding of the helical structure, along with base unstacking. We determined that the high-force transition that occurs in polydeoxyadenylic acid single-stranded DNA is caused by the cooperative forced flipping of the dihedral angle formed between four atoms, O5'-C5'-C4'-C3' (γ torsion), in the nucleic acid backbone within the canonical B-type helix. The γ torsion also flips under force in A-type helices, where the helix is shorter and wider as compared to the B-type helix, but this transition is less cooperative than in the B type and does not generate a high-force plateau in the force spectrums of A-type helices. We find that a similar high-force transition can be induced in polyadenylic acid single-stranded RNA by urea, presumably due to disrupting the intramolecular hydrogen bonding in the backbone. We hypothesize that a pronounced high-force transition observed for B-type helices of double stranded DNA also involves a cooperative flip of the γ torsion. These observations suggest new fundamental relationships between the canonical structures of single-and double-stranded DNA and the mechanism of their molecular elasticity.
Program in Computational Biology and Bioinformatics, Duke University, Durham, North Carolina 27708, USA.
Zackary N
ZN
Scholl
Mahir
M
Rabbi
David
D
Lee
Laura
L
Manson
Hanna
H
S-Gracz
Piotr E
PE
Marszalek
D004277:DNA, Single-Stranded / Q000737:chemistry*; D004548:Elasticity; D006860:Hydrogen Bonding; D018625:Microscopy, Atomic Force / Q000379:methods; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods
D004277:DNA, Single-Stranded; D012313:RNA