Small local variations in B-form DNA lead to a large variety of global geometries which can accommodate most DNA-binding protein motifs

<p>Abstract</p> <p>Background</p> <p>An important question of biological relevance is the polymorphism of the double-helical DNA structure in its free form, and the changes that it undergoes upon protein-binding. We have analysed a database of free DNA crystal structures to assess the inherent variability of the free DNA structure and have compared it with a database of protein-bound DNA crystal structures to ascertain the protein-induced variations.</p> <p>Results</p> <p>Most of the dinucleotide steps in free DNA display high flexibility, assuming different conformations in a sequence-dependent fashion. With the exception of the AA/TT and GA/TC steps, which are 'A-phobic', and the GG/CC step, which is 'A-philic', the dinucleotide steps show no preference for A or B forms of DNA. Protein-bound DNA adopts the B-conformation most often. However, in certain cases, protein-binding causes the DNA backbone to take up energetically unfavourable conformations. At the gross structural level, several protein-bound DNA duplexes are observed to assume a curved conformation in the absence of any large distortions, indicating that a series of normal structural parameters at the dinucleotide and trinucleotide level, similar to the ones in free B-DNA, can give rise to curvature at the overall level.</p> <p>Conclusion</p> <p>The results illustrate that the free DNA molecule, even in the crystalline state, samples a large amount of conformational space, encompassing both the A and the B-forms, in the absence of any large ligands. A-form as well as some non-A, non-B, distorted geometries are observed for a small number of dinucleotide steps in DNA structures bound to the proteins belonging to a few specific families. However, for most of the bound DNA structures, across a wide variety of protein families, the average step parameters for various dinucleotide sequences as well as backbone torsion angles are observed to be quite close to the free 'B-like' DNA oligomer values, highlighting the flexibility and biological significance of this structural form.</p

Curved DNA without AA/TT dinucleotide step.

The evidence is accumulating that dinucleotide steps other than AA/TT affect DNA flexure of AnTm (m + n greater than = 4) containing fragments. However, it is not clear whether macroscopic DNA flexure without AA/TT steps might occur. In this paper we demonstrate the anomaly in electrophoretic mobility of non AA/TT repetitive DNA sequences which is a function of sequence phasing. Therefore, our results show that PyPu (TA) and AG/CT steps, angulary separated by close to 180 degrees from Pu/Py (GC) and GG/CC steps, bend DNA, even in the absence of AnTm tracts