CONFORMATIONAL SPACE OF NUCLEIC ACIDS

Bohdan Schneider¹, Daniel Svozil²

¹Institute of Biotechnology AS CR, Vídeňská 1083, CZ-142 20 Prague, Czech Republic

²Institute of Chemical Technology, Technická 3, CZ-166 28 Prague, Czech Republic

Keywords: nucleic acids, DNA, RNA, conformation, torsion angles, structural bioinformatics

Past years brought up an information explosion of nucleic acid (NA) structures, mainly due to x-ray crystallography of large RNA molecules as ribosomal particles or various ribozymes. Several research groups including ours have systematically analyzed conformational space of RNA [1] and DNA [2]. These studies have laid firm foundation of description of NA structures at detailed dinucleotide level. Here we discuss the main features of observed RNA and DNA conformers and compare conformational behavior of RNA and DNA nucleotides.

Both DNA and RNA occur mostly in right-handed double helical forms, DNA in the B-form and RNA in the A-form. The vast majority of DNA dinucleotides form a bundle of similar conformers, which transform to one another in an almost continuous fashion. A number of B-type conformers concentrate around the “canonical” B-DNA, called BI and they transform by gradual torsional rotations to another major B-form, so called BII-DNA, and to the A-DNA form. B and A forms are connected via several A-to-BI sub-states with mixed structural properties including sugar puckers intermediate between the major C2’-endo and C3’-endo as O4'-endo and C1’-exo puckers. Bimodality of sugar puckers clearly pronounced in RNA is not observed in DNA and deoxyribose undergoes plastic, almost continuous transformation. The whole region B- and A-DNA conformers can be regarded as one broad right handed double helical form.

Several conclusions regarding sequence preferences for certain DNA conformers, as a preference of YR steps for adopting the BII-form, high propensity of the CG step for mixed A/B conformations, can be drawn and will be discussed in greater detail. Shown will also be how wrapping of DNA around histone proteins in a nucleosome-core particle is attained by a fairly regular alteration of BI and BII conformers, occasionally substituted by deformed BI or combined B/A conformers

In contrast to DNA, widely diverse RNA conformations seem to form isolate islands in the conformational space. The extra hydrogen bond donor and acceptor, the hydroxyl -O2’H at the ribose ring, stabilizes conformations that lead to bulges, loops, and consequently to RNA molecules globally folded in three dimensional space. When RNA is disrupted from its most stable AI form, it “jumps” to conformations incompatible with the rigid right handed helix. DNA, with its numerous, closely related conformers, is “soft”, whereas RNA, with fewer, but conformationally very different, conformers, is “rigid” but “brittle”. The definition of isolated RNA conformers [2], currently with about fifty distinct ‘rotamers’, allows for formulation of classification schema. The two-letter schema proposed by Richardson et al [2] is based on approximate values for all 7 torsion angles d-e-z-a-b-g-d between two ribose sugars; the first part of the modular conformer name is based on values of torsions d-e-z, used are numbers, the other part, described by letters, is based on a-b-g-d. Sugar-to-sugar unit in the most frequent RNA conformation, A-form, is described as 1a. An advantage of the schema is that it can be used in RNA structural bioinformatics. The tw-character backbone conformer names can be alternated with the base sequence to provide an information-rich string description of the combined linear sequence and structure in RNA molecules. For instance the UNCG tetraloop [3] can be described by the modular string N1aU1zN2[C6nG1aN.

This work has been supported by a grant LC512 from the Ministry of Education of the Czech Republic.

1. Murray LJ, Arendall 3rd WB, Richardson DC and Richardson JS: Proc. Natl. Acad. Sci. USA 100 (2003) 13904-13909. Hershkovitz E, Tannenbaum E, Howerton SB et al.: Nucl. Acids Res., 31 (2003) 6249-6257. Schneider B, Moravek Z and Berman HM: Nucl. Acids Res., 32 (2004) 1666-1677. Sykes MT and Levitt M: J. Mol. Biol. 351 (2005) 26-38.

2. Richardson JS, Schneider B, Murray LW et al. RNA, 14, 465-481.

3. Svozil D, Kalina J, Omelka M, and Schneider B: Nucleic Acids Res. (2008).

4. Ennifar E, Nikouline A, Tishchenko S et al.: J.Mol.Biol. 304 (2000) 35-42.