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Why RNA and DNA Have Different Structures
July 11th 2009 00:39
We learned about the double helix over 50 years ago with publication of the Watson Crick formulation (Watson and Crick 1953) and the fiber X-ray diffraction patterns of groups led by Maurice Wilkins (Wilkins and Randall 1953) and Rosalind Franklin (Franklin and Gosling 1953). Analysis of the diffraction pattern, especially the fibers of the hydrated B form, could be immediately interpreted as consistent with a double helix. The weakness of the first-layer line relative to the second and the virtual absence of the fourth-layer line clearly suggested two chains wrapping around each other with the phosphate groups on the outside. More complex and not answered at the time was the question of why there were two forms. What was the nature of the less-hydrated fibers that produced the better oriented and crystalline A form that could convert to the B form? In those days a half-century ago, fiber diffraction was the only way such large, elongated molecules could be studied. Generally, the patterns had rotational disorder around the fiber axis, which could be at the molecular level in the case of the B form and often involved crystalline segments in the A form. The diffraction patterns were limited in resolution, but it could be said that they were consistent with the formulation. Over the next several years, work by Maurice Wilkins and his colleagues gradually refined the nature of the double-helical model that could give rise to the increasingly detailed diffraction patterns. However, the diffraction pattern could not “prove” the structure of the molecule, as there were too little data.
The ribose sugar ring contains five atoms, but they cannot all lie in one plane, and at least one atom must be out-of-plane (Fig. 1).With the continued analysis of the fiber patterns, it became clear that the B form contained a ribose ring pucker in which the C2' atom was out-of-plane on the same side as the base (C2' endo). Because of that pucker, the phosphate groups were nearly 7 Å apart, yielding an extended polynucleotide chain. Study of the more complex A form led to the conclusion that the C3' atom was out-of-plane (C3' endo). In that conformation, the phosphate groups were about 5.8–6 Å apart. Thus, the sugar phosphate backbone was shortened, leading to a double helix in which the base pairs were slightly displaced from the center of the helix to produce a flatter helix and a somewhat thicker molecule. A relative scarcity of water molecules stabilized that conformation. It became clear that the normal conformation in the hydrated in vivo environment involved the C2' endo sugar pucker of B form DNA.
Source: RNA Towards Medicine 2009
Source: RNA Towards Medicine 2009
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