DNA Conformations and Their Sequence Preferences

Bohdan Schneider1 and Daniel Svozil2

 

1Institute of Biotechnology AS CR, v.v.i., Vídeòská 1083, CZ-142 20 Prague, Czech Republic
2Institute of Chemical Technology, Technická 3, CZ-166 28 Prague, Czech Republic

 

We analyzed phosphodiester backbone conformations of almost eight thousand DNA dinucleotides from about 500 carefully selected crystal structures containing naked and complexed DNA extracted from the Nucleic Acid Database (NDB, [1]). The analysis identified all the known major conformers of the B, A, and Z types thereby confirming the validity of the procedure but we also observed various intermediate BI/BII and B/A conformers. We investigated how the conformers build larger, often deformed or unusual DNA structures as bent or kinked DNA, tetraplexes, and junctions. To summarize, the BI-form (“canonical” B-form) is by far the most populated in both naked and complexed DNA, BII is a distinct B-form but both BI and BII are bridged in protein complexes by a series of intermediate conformers. We confirmed that DNA in protein complexes acquires quite frequently A-like conformations and even pure A-form.  Proteins in general broaden the DNA conformation space and induce existence of conformers not or rarely observed conformers as intermediate BI/BII or mixed B/A.

The wrapping of DNA around histone proteins in a nucleosome-core particle is achieved by a fairly regular alteration of BI and BII conformers, BII is occasionally substituted by deformed BI or B/A conformers. Even in the highly deformed histone-wrapped DNA two or more BII conformers follow each other in sequence only very rarely.

For naked DNA, we examined possible sequence preferences of various dinucleotide conformers by chi-square statistical tests. In the closely studied B-like duplexes, the conformers were grouped into five broad categories, BI, BII, A-to-B, B-to-A, and “non-classified”. We observed important sequence preferences between these conformers. Here we highlight just a few: Homogenous RR and YY steps (except GG) are over-represented in BI; TG and its Watson–Crick counterpart, CA, prefer BII; the CG and GC steps show a high propensity for mixed B/A conformations. The GC step shows mixed conformational preferences and many GC steps are structurally highly unusual; of all dinucleotides, this step has conformationally the most complicated behavior.

This study concludes our exploration of the conformational space of DNA [2] and RNA [3, 4] dinucleotides.

 

1.     Berman, H.M., Olson, W.K., Beveridge, D.L., Westbrook, J., Gelbin, A., Demeny, T., Hsieh, S.-H., Srinivasan, A.R. and Schneider, B. Biophys. J., 63 (1992) 751-759.

2.     DNA Conformations and Their Sequence Preferences. Daniel Svozil, Jan Kalina, Marek Omelka, and Bohdan Schneider. Nucleic Acids Res. 36, 3690-3704 (2008). doi: 

3.     RNA Backbone: Consensus All-angle Conformers and Modular String Nomenclature. Jane S. Richardson, Bohdan Schneider, Laura W. Murray, Gary J. Kapral, Robert M. Immormino, Jeffrey J. Headd, David C. Richardson, Daniela Ham, Eli Hershkovits, Loren Dean Williams, Kevin S. Keating, Anna Marie Pyle, David Micallef, John Westbrook, and Helen M. Berman. RNA, 14, 465-481 (2008).

4.     RNA Conformational Classes. Bohdan Schneider, Zdenìk Morávek, Helen M. Berman: Nucl.Acids Res. 32, 1666-1677 (2004).