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, pp. 603-607
Section 23.3.4.1.2. Helix bending
a
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095–1570, USA |
Sequence-dependent bendability has been reviewed recently by Dickerson (1988a,b,c) and Dickerson & Chiu (1997). The relative bendability of different regions of B-DNA sequence is an important aspect of recognition, one that is used by countless control proteins that must bind to a particular region of double helix. Catabolite activator protein or CAP (Schultz et al., 1991; Parkinson et al., 1996), lacI (Lewis et al., 1996) and purR (Schumacher et al., 1994) repressors, γδ-resolvase (Yang & Steitz, 1995), EcoRV restriction enzyme (Winkler et al., 1993; Kostrewa & Winkler, 1995), integration host factor or IHF (Rice et al., 1996), and TBP or TATA-binding protein (Kim, Gerger et al., 1993; Kim, Nikolov & Burley, 1993; Nikolov et al., 1996; Juo et al., 1996) are all sequence-specific DNA-binding proteins that bend or deform the nucleic acid duplex severely during the recognition process. IHF in Fig. 23.3.4.5 may be taken as representative of this class of DNA-binding proteins. The bend is produced by two localized rolls of ca 60° in a direction compressing the major groove and are additive, because they are spaced nine base pairs, or roughly one turn of helix, apart. In IHF, the two helix segments flanking the bend should be straight and unbent, and this is accomplished in one segment via a six-adenine A-tract: -C-A-A-A-A-A-A-G-.
The bending locus in IHF is C-A-A-T/A-T-T-G . It is C-G in lacI and purR repressors (Fig. 23.3.4.6), C-A = T-G in CAP (Fig. 10 of Dickerson, 1998b), and T-A in EcoRV, γδ-resolvase and TBP (Fig. 23.3.4.7). Pyrimidine-purine or Y-R steps appear to be especially suitable loci for roll bending. The dashed lines in Figs. 23.3.4.6 and 23.3.4.7 plot tilt, and demonstrate its insignificance in bending, compared with roll. (This is intuitively obvious. Imagine yourself standing near a tall stack of wooden planks in a lumberyard during an earthquake. Where would you prefer to stand: alongside the stack, or at one end?)
In summary, bending of the B-DNA helix nearly always involves roll, not tilt. The easier direction of bending is that which compresses the broad major groove, although examples of roll compression of the minor groove are known. Y-R steps are especially prone to roll bending. Again, the phenomenon is one of sequence-induced bendability, not mandatory bending. No one imagines that the IHF binding sequence of Fig. 23.3.4.5 is permanently kinked at its two C-A-A-T/A-T-T-G steps, wandering deformed through the nucleus, looking for an IHF molecule to bind to. Instead, this sequence has a potential bendability that other sequences, such as A-A-A-A-A-A, lack.
Table 23.3.4.1 summarizes the observed behaviour of Y-R, R-R and R-Y steps from a great many X-ray crystal structure analyses, with and without bound DNA. In the present context, these rules are termed the `Major Canon', since they are well established and generally well understood. Some understanding of the proneness of Y-R steps to bend can be obtained by looking at stereo pairs of two successive base pairs viewed down the helix axis. Fig. 23.3.4.8 gives a few representative examples; many more can be found in Figs. 4–6 of Dickerson (1988b) and in the original literature. In brief, Y-R steps, especially C-A and T-A, tend to orient so that polar exocyclic N and O atoms stack against polarizable rings of the other base pair. This is the same type of polar-on-polarizable stacking stabilization mentioned earlier in connection with O4′ and guanine in Z-DNA (Bugg et al., 1971; Thomas et al., 1982; Hunter & Sanders, 1990; B32). Base pairs in T-A steps tend not to slide over one another along their long axes, keeping pyrimidine O2 stacked over the purine five-membered ring (Fig. 23.3.4.8b). C-A steps can adopt this same stacking, or the base pairs can slide until the pyrimidine O2 sits over the purine six-membered ring instead (Fig. 23.3.4.8a).
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Purine-purine or R-R steps behave quite differently (Fig. 23.3.4.8c). They stack ring-on-ring, usually with greater overlap on the purine end than the pyrimidine. The net effect is that the pivot appears to pass through or near the purines, while pyrimidines at the other end of the pairs stack O2-on-ring as with Y-R steps. R-Y steps tend to stack ring-on-ring, with little contribution from exocyclic atoms.
El Hassan & Calladine (1997) have recently examined roll, slide and twist behaviour at 400 different steps observed in crystal structures of 24 A- and 36 B-DNA oligomers. The author has carried out a similar analysis of 1137 steps from 86 sequence-specific protein–DNA complexes (Dickerson, 1998a,c; Dickerson & Chiu, 1997). A striking feature is that trends in local parameters are just the same in DNA crystals and in protein–DNA complexes. The frequently invoked nightmare of `crystal packing deformations' appears to be of only minor significance. In both studies (El Hassan & Calladine, 1997; Dickerson, 1998b), roll versus slide, slide versus twist and twist versus roll plots are presented for all ten possible base-pair steps. Fig. 23.3.4.9 illustrates roll versus slide plots for two Y-R, two R-R and two R-Y steps.
Table 23.3.4.2 summarizes observations from these roll/slide/twist plots. These are labelled the `Minor Canon' since they are recent, approximate and not well understood. However, they provide goals for future investigations of helix behaviour.
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References
Bugg, C. E., Thomas, J. M., Sundaralingam, M. & Rao, S. T. (1971). Stereochemistry of nucleic acids and their constituents. X. Solid-state base-stacking patterns in nucleic acid consituents and polynucleotides. Biopolymers, 10, 175–219.Google ScholarDickerson, R. E. (1998a). Sequence-dependent B-DNA conformation in crystals and in protein complexes. In Structure, motion, interaction and expression of biological macromolecules, edited by R. H. Sarma & M. H. Sarma, pp. 17–36. New York: Adenine Press.Google Scholar
Dickerson, R. E. (1998b). Helix structure and molecular recognition by B-DNA. In Oxford handbook of nucleic acid structure, edited by S. Neidle, ch. 7, pp. 145–197. Oxford University Press.Google Scholar
Dickerson, R. E. (1998c). DNA bending: the prevalence of kinkiness and the virtues of normality. Nucleic Acids Res. 26, 1906–1926.Google Scholar
Dickerson, R. E. & Chiu, T. K. (1997). Helix bending as a factor in protein/DNA recognition. Biopolymers Nucleic Acid Sci. 44, 361–403.Google Scholar
El Hassan, M. A. & Calladine, C. R. (1997). Conformational characteristics of DNA: empirical classifications and a hypothesis for the conformational behaviour of dinucleotide steps. Philos. Trans. R. Soc. London A, 355, 43–100.Google Scholar
Hunter, C. A. & Sanders, J. K. M. (1990). The nature of π–π interactions. J. Am. Chem. Soc. 112, 5525–5534.Google Scholar
Juo, Z. S., Chiu, T. K., Leiberman, P. M., Baikalov, I., Berk, A. J. & Dickerson, R. E. (1996). How proteins recognize the TATA box. J. Mol. Biol. 261, 239–254.Google Scholar
Kim, J. L., Nikolov, D. B. & Burley, S. K. (1993). Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature (London), 365, 520–527.Google Scholar
Kim, Y., Geiger, J. H., Hahn, S. & Sigler, P. B. (1993). Crystal structure of a yeast TBP/TATA-box complex. Nature (London), 365, 512–520.Google Scholar
Kostrewa, D. & Winkler, F. K. (1995). Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 Å resolution. Biochemistry, 34, 683–696.Google Scholar
Lewis, M., Chang, G., Horton, N. C., Kercher, M. A., Pace, H. C., Schumacher, M. A., Brennan, R. G. & Lu, P. (1996). Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science, 271, 1247–1254.Google Scholar
Nikolov, D. B., Chen, H., Halay, E. D., Hoffman, A., Roeder, R. G. & Burley, S. K. (1996). Crystal structure of a human TATA box-binding protein/TATA element complex. Proc. Natl Acad. Sci. USA, 93, 4862–4867.Google Scholar
Parkinson, G., Wilson, C., Gunasekera, A., Ebright, Y. W., Ebright, R. H. & Berman, H. M. (1996). Structure of the CAP–DNA complex at 2.5 angstroms resolution: a complete picture of the protein–DNA interface. J. Mol. Biol. 260, 395–408.Google Scholar
Rice, P. A., Yang, S.-W., Mizuuchi, K. & Nash, H. A. (1996). Crystal structure of an IHF–DNA complex: a protein-induced DNA U-turn. Cell, 87, 1295–1306.Google Scholar
Schultz, S. C., Shields, G. C. & Steitz, T. A. (1991). Crystal structure of a CAP–DNA complex: the DNA is bent by 90 degrees. Science, 253, 1001–1007.Google Scholar
Schumacher, M. A., Choi, K. Y., Zalkin, H. & Brennan, R. G. (1994). Crystal structure of LacI member, PurR, bound to DNA: minor groove binding by alpha helices. Science, 266, 763–770.Google Scholar
Thomas, K. A., Smith, G. M., Thomas, T. B. & Feldmann, R. J. (1982). Electronic distributions within protein phenylalanine aromatic rings are reflected by the three-dimensional oxygen atom environments. Proc. Natl Acad. Sci. USA, 79, 4843–4847.Google Scholar
Winkler, F. K., Banner, D. W., Oefner, C., Tsernoglou, D., Brown, R. S., Heathman, S. P., Bryan, R. K., Martin, P. D., Petratos, K. & Wilson, K. S. (1993). The crystal structure of EcoRV endonuclease and of its complexes with cognate and non-cognate DNA fragments. EMBO J. 12, 1781–1795.Google Scholar
Yang, W. & Steitz, T. A. (1995). Crystal structure of the site-specific recombinase gamma delta resolvase complexed with a 34 bp cleavage site. Cell, 82, 193–207.Google Scholar