International
Tables for
Crystallography
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

© International Union of Crystallography 2006
International Tables for Crystallography (2006). Vol. F. ch. 23.3, p. 588   | 1 | 2 |

Section 23.3.1. Introduction

R. E. Dickersona*

a Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095–1570, USA
Correspondence e-mail: red@mbi.ucla.edu

23.3.1. Introduction

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In 1953, James Watson and Francis Crick solved the structure of double-helical DNA (Watson & Crick, 1953[link]; Crick & Watson, 1954[link]). So what has a dedicated cadre of X-ray crystallographers been doing for the subsequent 45 years? That is the subject of this chapter: the advance of our knowledge of nucleic acid duplexes, primarily from single-crystal X-ray diffraction, and the biological implications of this new knowledge. The focus will be primarily on DNA because much more is known about it, but DNA/RNA hybrids and duplex RNA will also be considered. Because the emphasis is on the geometry of the nucleic acid double helix, exotic structures, such as quadruplexes, hammerhead ribozymes and aptamers, will be omitted, as will larger-scale structures such as tRNA.

Fibre diffraction showed that there were two basic forms of DNA duplex: the common B form and a more highly crystalline A form (Fig. 23.3.1.1)[link] that, in some but not all sequences, could be produced by dehydrating the fibre (Franklin & Gosling, 1953[link]; Langridge et al., 1960[link]; Arnott, 1970[link]; Leslie et al., 1980[link]). A- and B-DNA are contrasted in Figs. 23.3.1.2[link] and 23.3.1.3[link]. The high-humidity B form has base pairs sitting squarely on the helix axis and roughly perpendicular to that axis. In contrast, in the low-humidity A form, the base pairs are displaced off the helix axis by ca 4 Å and are inclined 10–20° away from perpendicularity to that axis. The two grooves in B-DNA are of comparable depth because base pairs sit on the helix axis, but the major groove is wider than the minor because of asymmetry of attachment of base pairs to the backbone chains. In A-DNA, the minor groove is broad and shallow, whereas the major groove is cavernously deep (all the way from the surface of the helix, to the helix axis, and beyond) but can be quite narrow.

[Figure 23.3.1.1]

Figure 23.3.1.1| top | pdf |

`Hot wire' painting of A-DNA by Irving Geis. Geis produced two dramatic paintings of horse-heart cytochrome c, in which the sole light source was the central iron atom within the haem, producing a glowing `molecular lantern' effect. One painting showed this central luminous haem surrounded by hydrophobic side chains; the other featured the polar side chains extending out from the surface. These are to be seen today on the front and back covers of Voet & Voet's Biochemistry (Voet & Voet, 1990[link], 1995[link]). In the present A-DNA painting, Geis chose the imaginary central axis of the helix as a monofilament light source, thereby reversing the conventional illumination: atoms lining the deep major groove glow brightly, whereas the outer surface of the helix is in dark silhouette. Geis struggled with the B helix as an artistic subject, but was never satisfied with the results. Hence, this glowing A-DNA helix represents his nucleic acid artistic legacy. Reprinted courtesy of the estate of Irving Geis. Rights owned by Howard Hughes Medical Institute.

[Figure 23.3.1.2]

Figure 23.3.1.2| top | pdf |

Infinite A-DNA helix, generated from the X-ray crystal structure of the hexamer G-G-T-A-T-A-C-C (references A2 and A7 in Table A23.3.1.1[link]) by deleting the outer base pair from each end and stacking images of the resulting truncated hexamer so their outer phosphate groups overlapped. This generates an endless helix that exhibits the local structural features of the X-ray crystal structure. Note the degree to which the A helix resembles an antiparallel double-stranded ribbon wound around an invisible helical core (the `hot wire' axis of Fig. 23.3.1.1[link]). (From Dickerson, 1983[link].) Reprinted courtesy of the estate of Irving Geis. Rights owned by Howard Hughes Medical Institute.

[Figure 23.3.1.3]

Figure 23.3.1.3| top | pdf |

Infinite B-DNA helix, generated in a similar manner to Fig. 23.3.1.2[link] from the central ten base pairs of the dodecamer C-G-C-G-A-A-T-T-C-G-C-G (B1–B5). Note that the minor groove is narrow in the AT region facing the viewer at the centre, but appreciably wider in the GC regions on the back side of the helix at top and bottom. Propeller twisting, or deviations of bases from coplanarity within one pair, is one sequence-dependent aspect of DNA that was not suspected from the averaged structures obtained from fibres. (From Dickerson, 1983[link].) Reprinted courtesy of the estate of Irving Geis. Rights owned by Howard Hughes Medical Institute.

Pohl and co-workers had shown in the 1970s that alternating poly(dC-dG) is special in that it undergoes a reversible salt- or alcohol-induced conformation change (Pohl & Jovin, 1972[link]; Pohl, 1976[link]). Hence, it was not surprising that when DNA synthesis methods advanced to the stage where oligonucleotide crystallization became feasible, two separate research groups – those of Alexander Rich at MIT and Richard Dickerson at Caltech – elected to synthesize, crystallize and solve a short, alternating C-G oligomer. The result was a third family of DNA duplexes, Z-DNA (Fig. 23.3.1.4)[link], first as the hexamer C-G-C-G-C-G (Z1) and then the tetramer C-G-C-G (Z3). (References to A-, B- and Z-DNA structures are listed at the end of Tables A23.3.1.1[link], A23.3.1.2[link] and A23.3.1.3[link] in the Appendix[link], respectively. They are cited by numbers beginning with A, B or Z.) Single-crystal analyses of the traditional helix types soon followed: B-DNA as C-G-C-G-A-A-T-T-C-G-C-G (B1), and A-DNA as both C-C-G-G (A1) and G-G-T-A-T-A-C-C (A2).

[Figure 23.3.1.4]

Figure 23.3.1.4| top | pdf |

Infinite Z-DNA helix, generated as before from the central four base pairs of the hexamer C-G-C-G-C-G (Z1). G and C bases alternate along each chain. The sugar–phosphate backbone adopts a pronounced zigzag pathway, rising vertically past each guanine, but travelling horizontally across the helix at cytosines. Hence, the formal helix repeat is two base pairs, G followed by C, rather than a single base pair, as in the A and B helices. Note that the structures of Z-DNA and A-DNA are in many ways the inverse of one another. The Z helix is left-handed, tall and slim, with a deep minor groove, a flattened major groove and small propeller twist. The A helix is right handed, short and broad, with a deep major groove, a shallow minor groove and large propeller twist. (From Dickerson, 1983[link].) Reprinted courtesy of the estate of Irving Geis. Rights owned by Howard Hughes Medical Institute.

References

First citation Arnott, S. (1970). The geometry of nucleic acids. Prog. Biophys. Mol. Biol. 21, 265–319. Google Scholar
 First citation Crick, F. H. C. & Watson, J. D. (1954). The complementary structure of deoxyribonucleic acid. Proc. R. Soc. London Ser. A, 223, 80–96.Google Scholar
 First citation Franklin, R. E. & Gosling, R. G. (1953). The structure of sodium thymonucleate fibres. I. The influence of water content. Acta Cryst. 6, 673–677.Google Scholar
 First citation Langridge, R., Marvin, D. A., Seeds, W. E., Wilson, H. R., Hooper, C. W., Wilkins, M. H. F. & Hamilton, L. D. (1960). The molecular configurations of deoxyribonucleic acid. II. Molecular models and their Fourier transforms. J. Mol. Biol. 2, 38–64.Google Scholar
 First citation Leslie, A. G. W., Arnott, S., Chandrasekaran, R. & Ratliff, R. L. (1980). Polymorphism of DNA double helices. J. Mol. Biol. 143, 49–72.Google Scholar
 First citation Pohl, F. M. (1976). Polymorphism of a synthetic DNA in solution. Nature (London), 260, 365–366.Google Scholar
 First citation Pohl, F. M. & Jovin, T. M. (1972). Salt-induced co-operative conformational change of a syhnthetic DNA: equlibrium and kinetic studies with poly(dG-dC). J. Mol. Biol. 67, 375–396.Google Scholar
 First citation Watson, J. D. & Crick, F. H. C. (1953). Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature (London), 171, 737–738.Google Scholar








































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