Abstract
Of the DNA-binding motifs, the (Cys)2(His)2-type zinc finger motif has great potential for manipulation. The zinc finger motif offers an attractive framework for the design of novel DNA-binding proteins. Specially, a structure-based design strategy is valuable for the creation of new artificial zinc finger proteins that have novel DNA-binding properties, namely, long-DNA recognition, DNA bending, and AT-rich sequence recognition. Herein, new strategies for the design of multi-zinc finger proteins for the recognition of a target DNA sequence, a DNA-bending zinc finger protein, a (His)4-type zinc finger protein, and an AT-recognizing zinc finger protein are described based on recent experimental results.
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Nagaoka, M. and Sugiura, Y. (2000) Artificial zinc finger peptides: creation, DNA recognition, and gene regulation. J. Inorg. Biochem. 82, 57–63.
Imanishi, M., Hori, Y., Nagaoka, M., and Sugiura, Y. (2001) Design of novel zinc finger proteins: towards artificial control of specific gene expression. Eur. J. Pharm. Sci. 13, 91–97.
Pabo, C. O., Peisach, E., and Grant, R. A. (2001) Design and selection of novel Cys2His2 zinc finger proteins. Annu. Rev. Biochem. 70, 313–340.
Pavletich, N. P. and Pabo, C. O. (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 Å. Science 252, 809–816.
Pavletich, N. P. and Pabo, C. O. (1993) Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science 261, 1701–1707.
Kim, C. A. and Berg, J. M. (1996) A 2.2 Å resolution crystal structure of a designed zinc finger protein bound to DNA. Nat. Struct. Biol. 3, 940–945.
Nolte, R. T., Conlin, R. M., Harrison, S. C., and Brown, R. S. (1998) Differing roles for zinc fingers in DNA recognition: structure of a six-finger transcription factor IIIA complex. Proc. Natl. Acad. Sci. USA 95, 2938–2943.
Wütrich, K. (1986) NMR of Proteins and Nuleic Acids. Wiley Interscience, New York, NY.
Kuwahara, J. and Coleman, J. E. (1990) Role of the zinc(II) ions in the structure of the three-finger DNA binding domain of the Sp1 transcription factor. Biochemistry 29, 8627–8631.
Kamiuchi, T., Abe, E., Imanishi, M., Kaji, T., Nagaoka, M., and Sugiura, Y. (1998) Artificial nine zinc-finger peptide with 30-base-pair binding sites. Biochemistry 37, 13,827–13,834.
Imanishi, M., Hori, Y., Nagaoka, M., and Sugiura, Y. (2000) DNA-bending finger: artificial design of 6-zinc finger peptides with polyglycine linker and induction of DNA bending. Biochemistry 39, 4383–4390.
Hori, Y., Suzuki, K., Okuno, Y., Nagaoka, M., Futaki, S., and Sugiura, Y. (2000) Artificial zinc finger peptide containing a novel His4 domain. J. Am. Chem. Soc. 122, 7648–7653.
Nagaoka, M., Doi, Y., Kuwahara, J., and Sugiura, Y. (2002) Novel strategy for the design of a new zinc finger: creation of a zinc finger for the AT-rich sequence by α-helix substitution. J. Am. Chem. Soc. 124, 6526–6527.
Imanishi, M. and Sugiura, Y. (2002) Artificial DNA-bending six-zinc finger peptides with different charged linkers: Distinct kinetic properties of DNA binding. Biochemistry 41, 1328–1334.
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© 2007 Humana Press Inc.
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Nomura, W., Sugiura, Y. (2007). Design and Synthesis of Artificial Zinc Finger Proteins. In: Arndt, K.M., Müller, K.M. (eds) Protein Engineering Protocols. Methods in Molecular Biology™, vol 352. Humana Press. https://doi.org/10.1385/1-59745-187-8:83
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DOI: https://doi.org/10.1385/1-59745-187-8:83
Publisher Name: Humana Press
Print ISBN: 978-1-58829-072-4
Online ISBN: 978-1-59745-187-1
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