Protein–Nucleic Acid Interaction: Major Groove Recognition Determinants


Protein–nucleic acid interactions play a crucial role in central biological processes. It is known that the most common binding element of proteins is an α helix and the primary binding site on DNA is in the major groove. Some general rules of the α helix binding to the DNA major groove have been derived, but there is no general code (one‐to‐one correspondence) for recognition.

Keywords: protein–nucleic acid complexes; zinc finger; α helix binding; major groove interactions

Figure 1.

α Helix binding to the major groove of DNA. Two views (90° apart) of a helix–turn–helix (HTH) motif are shown. Reproduced from Matthews, .

Figure 2.

Docking of α helix in the major groove, the accessible area in the major groove is highlighted in red.

Figure 3.

(a) The ββα folding of Cys2His2 zinc finger motif. Reproduced from Wolfe et al. (b) Binding of the zinc finger in the major groove of DNA.

Figure 4.

Docking of the α helices in the major groove. The recognition helix of the i + 3 superfamily is shown in yellow and that of the i + 4 superfamily in red. Reproduced from Pabo and Nekludova .

Figure 5.

Interactions in Zif268 zinc finger–DNA complex. (a) Cartoon representation of the complex. (b). Schematic illustration of the contacts between the fingers and the DNA bases. Arrows indicate hydrogen‐bonding interactions and circles represent van der Waals contacts. (c) Side‐chains forming hydrogen‐bonding interaction to G•C base pairs. Reproduced from Pavletich and Pabo ; Wolfe et al. .



Harrison SC (1991) A structural taxonomy of DNA‐binding domains. Nature 353: 715–719.

Luisi BF (1995) DNA–protein interaction at high resolution. In: Lilly DMJ (ed.) DNA–Protein Structural Interactions, pp. 1–48. Oxford: Oxford University Press.

Luscombe N, Austin SE, Berman HM and Thornton JM (2000) An overview of the structures of protein–DNA complexes. Genome Biology 1: 1–37.

Matthews BW (1988) No code for recognition. Nature 355: 294–295.

Miller DL, McLachlan AD and Klug A (1985) Repetitive zinc‐binding domains in the protein transcription factor IIIA from Xenopusoocytes. EMBO Journal 4: 1609–1614.

Nadassy K, Wodak SJ and Janin J (1999) Structural features of protein–nucleic acid recognition sites. Biochemistry 38: 1999–2017.

Ohlendorf DH, Anderson WF, Fisher RG, Takeda Y and Matthews BW (1982) The molecular basis of DNA–protein recognition inferred from the structure of crorepressor. Nature 298: 718–713.

Pabo CO and Nekludova L (2000) Geometric analysis and comparison of protein–DNA interfaces: why is there no simple code for recognition? Journal of Molecular Biology 301: 597–624.

Pavletich NP and Pabo CO (1991) Zinc finger‐DNA recognition: crystal structure of a Zif268–DNA complex at 2.1 Å. Science 252: 809–817.

Seeman NC, Rosenberg JM and Rich A (1976) Sequence‐specific recognition of double helical nucleic acids by proteins. Proceedings of the National Academy of Sciences of the USA 73: 804–808.

Steitz TA (1990) Structural studies of protein–nucleic acid interaction: the sources of sequence‐specific binding. Quarterly Review of Biophysics 23: 205–280.

Sundaralingam M (1975) Structure and conformation of nucleosides and nucleotides and their analogs as determined by x‐ray diffraction. Annals of the New York Academy of Sciences 255: 3–42.

Sundaralingam M and Burkhart B (1997) Protein–nucleic acid interactions: general principles. In: Parthasarathy S and Glusker JP (eds) Aspects of Crystallography in Molecular Biology, pp. 363–390. New Delhi: New Age International Publishers.

Wolfe SA, Nekludova L and Pabo CO (1999) DNA recognition by Cys2His2 zinc finger proteins. Annual Review of Biophysical Biochemical Structures 3: 183–212.

Further Reading

Branden C and Tooze J (1991) Introduction to Protein Structure. New York and London: Garland Publishing, Inc.

Lilley DMJ (Ed.) (1995) DNA–Protein: Structural Interactions. New York: Oxford University Press.

Saluz HP and Wiebauer K (1995) DNA and Nucleoprotein Structure in vivo. Austin, TX: R. G. Landes Company.

Saenger W (1984) Principle of Nucleic Acid Structure. New York: Springer–Verlag.

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Xiong, Yong, and Sundaralingam, Muttaiya(Apr 2001) Protein–Nucleic Acid Interaction: Major Groove Recognition Determinants. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0003138]