CONFORMATIONAL SPACE OF NUCLEIC ACIDS

Bohdan Schneider, Daniela Ham, Daniel Svozil

Centre for Biomolecules and Complex molecular Systems, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, Fleming Square 2, 166 10 Prague 6, Czech Republic

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

Explosion of information on nucleic acid (NA) structure available in the public archive [1] has enabled detailed analyses of NA, mostly RNA, conformational space [2-5]. The RNA Ontology Consortium, ROC [6], is a collaborative framework that coordinates effort of several research groups to lay firm foundation to description of RNA structure. Consensual description of RNA backbone conformations sponsored by the ROC is before finish [Richardson et al. in preparation, 2007]. To complement the analysis of RNA conformations, we investigated conformations of more than eight thousand nucleotides from over four hundred well resolved DNA x-ray structures. Here we compare basic features of conformational behavior of RNA and DNA nucleotides.

For both DNA and RNA, the double helical A and B forms represent a large majority of populations. In the DNA conformational space, gradual changes lead from A forms with C2’-endo sugar puckers to B forms with C3’-endo sugars and several A-to-BI sub-states with mixed sugar puckers were identified. Existence of intermediates with deoxyribose in the O4'-endo region was detected not only in protein/DNA complexes but significantly also in high resolution structures of naked DNA. There are also sub-states of the BI and especially BII conformations, most are induced by interactions with other molecules, mostly proteins. All these conformational sub-states or intermediates keep the basic double helical arrangement. For instance, DNA in complex with histone core particles acquires its circular shape by a combining nucleotides in the BI and BII conformations. DNA bound to TATA-box binding proteins seems to be extremely deformed, opens up its minor groove and bends away from the protein but it keeps its double helical arrangement and only locally changes from B to A type. In summary, DNA undergoes “plastic deformation” and its conformation can be changed from right-handed double helix only under very specific circumstances and into a few structurally defined states, as specific sequence can form G-tetraplexes or a certain sequence can form Z form DNA at high salt.

In contrast, 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 A form, it “jumps” to conformations incompatible with the rigid right handed helix.

This work has been supported by an NSF grant DBI 0110076 to the NDB and by a grant LC512 from the Ministry of Education of the Czech Republic.

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