Abstract
BackgroundAn 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.ResultsMost 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.ConclusionThe 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.
Highlights
An important question of biological relevance is the polymorphism of the doublehelical DNA structure in its free form, and the changes that it undergoes upon protein-binding
The present analysis provides some interesting insights into the conformational flexibility of the DNA molecule, and reveals that many of the conformations observed in bound DNA, both at the local dinucleotide step level, and the gross structural level, are accessible to unbound DNA, while a few conformations are solely induced by protein binding
The HTH dataset consists of DNA bound by a wide variety of proteins ranging across 22 SCOP [78] classes, and includes 3 ternary TATA Binding Protein-Transcription Factor IIB-TATA-box complexes and 6 Catabolite Activator Protein-DNA complexes
Summary
An important question of biological relevance is the polymorphism of the doublehelical DNA structure in its free form, and the changes that it undergoes upon protein-binding. The first crystal structure of a B-form DNA was solved in 1981 [8], and was found to have significant sequence-dependant variability, with an average roll per dinucleotide step of 0.5 ± 5.2°, an average local helical twist of 35.6 ± 4.4° and an average slide of 0.2 ± 0.5 Å. Several other forms of synthetic DNA were solved, which did not fit the canonical A-like or B-like conformation [2] Against this wide ranging polymorphism of the double-helical DNA molecule, at the dinucleotide step level, the RNA duplex crystal structures, that were solved around the same time [19,20,21,22,23,24], stood out for their rigidity, and their conformational proximity to the ARNA fibre model, independent of the sequence.
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