Comparison between A-DNA, B-DNA and Z-DNA

 

Introduction

DNA is a flexible double-helical molecule that can adopt more than one three-dimensional conformation. The best-known forms are A-DNA, B-DNA and Z-DNA. These conformations differ in helical direction, diameter, number of base pairs per turn, pitch, sugar pucker, groove geometry and the orientation of the bases relative to the helix axis. The particular form adopted by DNA depends on nucleotide sequence, hydration, ionic conditions, supercoiling and interactions with proteins or other molecules. B-DNA is the predominant form under normal physiological conditions, whereas A-DNA and Z-DNA become favored under particular environmental or structural conditions.

Understanding these three forms is important because DNA structure is not merely a static framework for genetic information. Changes in helix geometry can influence protein binding, transcription, chromatin organization, DNA recognition and the response of nucleic acids to changes in the cellular environment. The following comparison summarizes the principal structural and functional differences among A-DNA, B-DNA and Z-DNA.

Detailed comparison

Feature	A-DNA	B-DNA	Z-DNA
Helical sense	Right-handed	Right-handed	Left-handed
General shape	Short, broad and compact	Longer, slender and regular	Slender helix with a zig-zag backbone
Approx. diameter	About 23 Å (2.3 nm)	About 20 Å (2.0 nm)	About 18 Å (1.8 nm)
Base pairs per turn	About 11	About 10–10.5	About 12
Helical pitch	About 28 Å (2.8 nm)	About 34 Å (3.4 nm)	About 44–45 Å (4.4–4.5 nm)
Rise per base pair	About 2.6 Å	About 3.4 Å	About 3.7 Å
Base-pair orientation	Base pairs are markedly tilted relative to the helix axis	Base pairs are nearly perpendicular to the helix axis	Base pairs are arranged in an alternating geometry characteristic of the left-handed helix
Sugar pucker	Predominantly C3'-endo	Predominantly C2'-endo	Alternates; purines commonly C3'-endo and pyrimidines C2'-endo
Glycosidic bond	Bases are mainly in anti conformation	Bases are mainly in anti conformation	Alternates: purines are commonly syn and pyrimidines anti
Major groove	Deep and narrow	Wide and deep; readily accessible to many DNA-binding proteins	Flattened or poorly defined
Minor groove	Broad and shallow	Narrower than the major groove	Narrow and deep
Phosphate backbone	Smooth right-handed course	Smooth right-handed course	Distinctive zig-zag course, giving Z-DNA its name
Favored conditions	Low hydration and some protein-bound or RNA-containing duplexes	High hydration and ordinary physiological conditions	Alternating purine-pyrimidine sequences, high ionic strength, negative supercoiling and some chemical modifications such as cytosine methylation
Typical sequence preference	No strict repeating sequence requirement	No strict repeating sequence requirement	Often favored by alternating GC-rich sequences such as (CG)n
Common occurrence	Dehydrated DNA; double-stranded RNA and DNA-RNA hybrids often adopt an A-like geometry	Most chromosomal DNA in living cells	Transiently in negatively supercoiled DNA and at particular genomic regions
Biological relevance	Important for understanding RNA duplexes, DNA-RNA hybrids and nucleic-acid recognition	Principal structural form for storage and expression of genetic information	Associated with DNA topology, transcriptional activity, protein recognition and regulation in particular contexts

A-DNA

A-DNA is a right-handed double helix that is shorter and broader than the classical B form. It is favored when DNA is relatively dehydrated and is also closely related to the geometry normally adopted by double-stranded RNA and many DNA-RNA hybrid helices. The helix contains approximately 11 base pairs per turn, has a pitch of about 28 Å and a diameter of roughly 23 Å. Because the rise per base pair is only about 2.6 Å, the molecule appears comparatively compact along its longitudinal axis.

A characteristic feature of A-DNA is the marked inclination of the base pairs relative to the helix axis. The deoxyribose sugars predominantly show the C3'-endo pucker, and the bases generally remain in the anti glycosidic orientation. The major groove is deep and narrow, while the minor groove is broad and shallow. These features distinguish A-DNA clearly from B-DNA and alter the accessibility of the DNA surface to proteins and other ligands.

The A form is not considered the dominant configuration of ordinary chromosomal DNA under normal cellular hydration. Nevertheless, it is biologically important because A-like geometry is common in RNA duplexes, in DNA-RNA hybrids produced during transcription, and in particular nucleic-acid-protein complexes. Thus, A-DNA is especially useful for understanding the structural continuity between DNA and RNA helices.

B-DNA

B-DNA is the classical Watson-Crick form and is the predominant conformation of DNA under normal physiological conditions. It is a right-handed double helix with an average diameter of about 20 Å. A complete turn contains approximately 10 to 10.5 base pairs, the pitch is about 34 Å, and adjacent base pairs are separated by approximately 3.4 Å. The base pairs are positioned almost perpendicular to the helical axis, giving B-DNA a regular and relatively elongated appearance.

The sugar residues in B-DNA predominantly adopt the C2'-endo conformation, while the glycosidic bonds of the bases are generally anti. B-DNA possesses clearly defined major and minor grooves. The major groove is relatively wide and provides an information-rich surface on which many DNA-binding proteins can recognize specific base sequences without separating the strands. The minor groove is narrower and is also used by a range of proteins and small molecules for recognition.

The biological importance of B-DNA is fundamental. It provides the principal structural framework for the storage, replication and transcription of genetic information. Most descriptions of DNA-protein recognition, nucleosome formation, restriction-enzyme binding and sequence-specific transcription-factor binding use B-DNA as the reference conformation. The ability of B-DNA to undergo local bending, twisting, unwinding and transitions into other helical forms adds further structural flexibility to the genome.

Z-DNA

Z-DNA is structurally distinct because it forms a left-handed double helix. Its name is derived from the zig-zag course of the sugar-phosphate backbone. Z-DNA is narrower than the A and B forms, with a diameter of about 18 Å. It contains approximately 12 base pairs per turn and has a pitch of about 44 to 45 Å. The rise per base pair is approximately 3.7 Å. Rather than displaying the smooth backbone characteristic of right-handed DNA, alternating nucleotide conformations give the helix its characteristic zig-zag appearance.

Z-DNA frequently occurs in sequences containing alternating purines and pyrimidines, especially alternating guanine and cytosine residues. Its glycosidic conformations alternate: purines, particularly guanine, commonly adopt the syn orientation, whereas pyrimidines remain anti. The sugar puckers also alternate, with purine residues commonly showing C3'-endo and pyrimidines C2'-endo conformations. The major groove is flattened or poorly defined, while the minor groove is narrow and deep.

The Z conformation can be promoted by high ionic strength, negative supercoiling, particular nucleotide sequences and some chemical modifications such as cytosine methylation. In cells, Z-DNA is generally regarded as a transient or locally stabilized structure rather than the universal form of genomic DNA. Formation of Z-DNA has been associated with transcriptionally active regions, torsional stress and binding by specialized Z-DNA-recognizing proteins. For this reason, Z-DNA is important in studies of DNA topology, genome regulation and structural transitions in nucleic acids.

Major points of distinction

The simplest distinction among the three forms concerns helical direction. Both A-DNA and B-DNA are right-handed, whereas Z-DNA is left-handed. A-DNA is the broadest of the three forms, B-DNA has an intermediate diameter, and Z-DNA is the narrowest. A-DNA is relatively compact because the base pairs rise by a smaller distance along the helical axis, whereas B-DNA has the familiar 3.4 Å spacing between adjacent base pairs. Z-DNA differs additionally through its alternating syn and anti glycosidic conformations and its zig-zag phosphate backbone.

Their groove patterns are also diagnostically important. B-DNA possesses a well-developed major groove that is highly suitable for sequence-specific protein recognition. A-DNA has a deep, narrow major groove and a broad, shallow minor groove. In Z-DNA, the major groove is greatly reduced or flattened and the minor groove is narrow and deep. Therefore, conversion from one DNA form to another changes not only the overall dimensions of the helix but also the chemical surfaces available for molecular recognition.