Overview of the Structure of All-AT Oligonucleotides: Organization in Helices and Packing Interactions

Abstract

We present the crystalline organization of 33 all-AT deoxyoligonucleotide duplexes, studied by x-ray diffraction. Most of them have very similar structures, with Watson-Crick basepairs and a standard average twist close to 36 degrees. The molecules are organized as parallel columns of stacked duplexes in a helical arrangement. Such organization of duplexes is very regular and repetitive: all sequences show the same pattern. It is mainly determined by the stacking of the terminal basepairs, so that the twist in the virtual TA base step between neighbor duplexes is always negative, approximately -22 degrees. The distance between the axes of parallel columns is practically identical in all cases, approximately 26 A. Interestingly, it coincides with that found in DNA viruses and fibers in their hexagonal phase. It appears to be a characteristic distance for ordered parallel DNA molecules. This feature is due to the absence of short range intermolecular forces, which are usually due to the presence of CG basepairs at the end of the oligonucleotide sequence. The duplexes apparently interact only through their diffuse ionic atmospheres. The results obtained can thus be considered as intermediate between liquid crystals, fibers, and standard crystal structures. They provide new information on medium range DNA-DNA interactions.

DNA-Based Soft Phases

“…The stacking of nucleobases has been found to be involved in several DNA selfassembly processes, promoting the formation of DNA-DNA and DNA-protein complexes in vivo [44,45], driving end-to-end interactions of DNA double-and triple-helices in semi-dilute solutions [46], or determining the geometry of DNA 240 T. Bellini et al oligonucleotide crystals [47,48]. Stacking is also at the origin of the self-assembly processes leading to linear aggregation and LC ordering in solutions of guanosine quartets [49].…”

Polymorphic crystal structures of an all‐AT DNA dodecamer

“…This is achieved by increasing the MPD concentration and lowering the temperature of crystallization. However, in the case of all‐AT oligonucleotides, and in particular in the present case, this process either disrupted the crystals or changed the structural form obtained. Amorphous precipitates and phase separation were often found.…”

“…In the case of Form IV, the data could be tentatively processed with the XDS program, in spite of limited resolution. Molecular replacement was done with AmoRe, using a HASO column as search model in order to obtain an approximate solution.…”

“…We will present our results starting with the less ordered structures and finish with those structures which have a more stable crossed structure. We should note that in all previous studies of all‐AT oligonucleotide duplexes, they were found to crystallize as parallel columns of stacked DNA duplexes (HASO columns). Here for the first time we have detected crystal structures in which crossed duplexes are found.…”

“…Some time ago we obtained crystals with related oligonucleotides and discovered the Hoogsteen form of DNA . Since then we have studied many other all‐AT oligonucleotides, in an attempt to understand the polymorphism of this type of sequences . All‐AT DNA is unique, in the sense that no external crosslinking interactions mediated by ions are expected.…”