A DNA structural alphabet provides new insight into DNA flexibility

Bohdan Schneider,Jiří Černý,Paulína Božíková,Daniel Svozil,Petr Čech,Iva Nečasová

doi:10.1107/s2059798318000050

Abstract

DNA is a structurally plastic molecule, and its biological function is enabled by adaptation to its binding partners. To identify the DNA structural polymorphisms that are possible in such adaptations, the dinucleotide structures of 60 000 DNA steps from sequentially nonredundant crystal structures were classified and an automated protocol assigning 44 distinct structural (conformational) classes called NtC (for Nucleotide Conformers) was developed. To further facilitate understanding of the DNA structure, the NtC were assembled into the DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and the projection of CANA onto the graphical representation of the molecular structure was proposed. The NtC classification was used to define a validation score called confal, which quantifies the conformity between an analyzed structure and the geometries of NtC. NtC and CANA assignment were applied to analyze the structural properties of typical DNA structures such as Dickerson-Drew dodecamers, guanine quadruplexes and structural models based on fibre diffraction. NtC, CANA and confal assignment, which is accessible at the website https://dnatco.org, allows the quantitative assessment and validation of DNA structures and their subsequent analysis by means of pseudo-sequence alignment. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Acta_Cryst_D:2.

Highlights

The prevailing DNA architecture, a right-handed double helix composed of sequentially complementary antiparallel strands, is structurally very plastic
We demonstrate the usefulness of the NtC and CANA classification scheme by annotating a few prototypical DNA structures
We first characterize the structural properties of 44 distinct step-conformer classes called NtC (Nucleotide Conformers; the full list is given in Supplementary Table S1) and introduce a coarser yet comprehensive classification of DNA conformations: a structural alphabet called CANA (Conformational Alphabet of Nucleic Acids; Table 1, Fig. 3)

Summary

Introduction

The prevailing DNA architecture, a right-handed double helix composed of sequentially complementary antiparallel strands, is structurally very plastic. The DNA strand has the ability to accommodate large conformational changes by forming kinks or bends or to undergo radical rearrangements into loops or folded forms such as quadruplexes. These conformational changes cannot be understood without going beyond the ‘A–B–Z’ classification traditionally used to describe DNA structural diversity. The necessity of understanding the DNA conformational space in its full complexity increases with the increasing number of biologically important DNA structures other than the double helix: tetraplexes with complicated and variable topologies, single-stranded hairpins and cruciforms, and DNA junctions involved in recombinant processes such as Holliday junctions.

Methods

Results

Conclusion