Section 23.3.3.6. Biological applications of A, B and Z helices

The B helix is the biologically relevant structure for DNA. The A form might logically be adopted at the stage of transient DNA–RNA duplexes during transcription, but elsewhere the B form holds sway. It was once thought that binding of DNA to a protein surface, most particularly nucleosomal winding, might constitute a sufficient dehydration of bound water molecules from the DNA duplex to shift it to the A form. This proved to be false; nucleosomal DNA clearly retains the B conformation. The closest that one comes to biological A-DNA is local deformations upon binding of B-DNA to a few proteins that have been described as `A-like distortions'. On the other hand, the A helix has been found repeatedly in RNA duplexes, including tRNA and ribozymes.

The situation is even more restrictive with the Z helix. Although its alternating purine/pyrimidine sequence makes it unusable for genetic coding, the suggestion has been made on many occasions that Z-DNA might be an important element in genetic control by being involved in negative supercoiling (Herbert & Rich, 1996). It has been shown that a left-handed DNA conformation can be induced by negative superhelical stress, but it is not absolutely clear that this induced, left-handed conformation is the same as the Z helix seen in crystal structures of small oligomers. As noted by Herbert & Rich (1996), after nearly twenty years of enquiry, it is still far from certain that Z-DNA itself has any demonstrable biological role.¹

A major stumbling block is the cumbersome mechanism that must be invoked to explain a B-to-Z interconversion. As mentioned previously, a simple twisting of the helix from right to left is not sufficient, because the backbone chains run in opposite directions in the two forms. Fig. 23.3.3.6 demonstrates the steps that must still be undertaken after both B and Z helices have been unwound so as to remove all of their helical character. Note the opposite sense of the backbone strands in B [part (a)] and Z [part (e)]. In order to accomplish the interconversion, base pairs of B-DNA must be pulled apart, as in part (b), and each base pair swung around to the opposite side of the backbone `ladder' [part (c)]. This would automatically lead to syn conformations at both ends of the base pair, as drawn in Fig. 23.3.3.4(b). Returning pyrimidines to an anti conformation would create the zigzag backbone chain (Fig. 23.3.3.4c). Base pairs can then be re-stacked, as in parts (d) and (e) in Fig. 23.3.3.6 (which differ only by rotation of the entire helix about the vertical), to yield the backbone geometry of a Z helix. This is the simplest interconversion and one which was recognized and proposed in the very first Z-DNA structure paper (Z1). Other alternatives have been suggested, involving breaking individual base pairs, swinging the bases independently around their backbone chains, and re-forming the pairs. But one kind of special mechanism or another must be invoked if a B-to-Z interconversion is to be achieved.

Figure 23.3.3.6| top | pdf | Interconversion of a B to a Z helix. Because the strands have opposite directions in B (a) and Z (e), interconversion must involve opening up the helix (b), flipping each base pair to the other side (c), and re-stacking base pairs (d). (d) and (e) are identical upon rotation about a vertical axis.