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High-resolution structures of variant Zif268-DNA complexes: implications for understanding zinc finger-DNA recognition.

Elrod-Erickson M, Benson TE, Pabo CO
Structure 6 451-64 (1998)
Related entries: 1a1f, 1a1h, 1a1i, 1a1j, 1a1k, 1a1l, 1aay, 1zaa

Cited: 111 times
EuropePMC logo PMID: 9562555

Abstract

Background

Zinc fingers of the Cys2-His2 class comprise one of the largest families of eukaryotic DNA-binding motifs and recognize a diverse set of DNA sequences. These proteins have a relatively simple modular structure and key base contacts are typically made by a few residues from each finger. These features make the zinc finger motif an attractive system for designing novel DNA-binding proteins and for exploring fundamental principles of protein-DNA recognition.

Results

Here we report the X-ray crystal structures of zinc finger-DNA complexes involving three variants of Zif268, with multiple changes in the recognition helix of finger one. We describe the structure of each of these three-finger peptides bound to its corresponding target site. To help elucidate the differential basis for site-specific recognition, the structures of four other complexes containing various combinations of these peptides with alternative binding sites have also been determined.

Conclusion

The protein-DNA contacts observed in these complexes reveal the basis for the specificity demonstrated by these Zif268 variants. Many, but not all, of the contacts can be rationalized in terms of a recognition code, but the predictive value of such a code is limited. The structures illustrate how modest changes in the docking arrangement accommodate the new sidechain-base and sidechain-phosphate interactions. Such adaptations help explain the versatility of naturally occurring zinc finger proteins and their utility in design.

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Related citations provided by authors (3)

  1. Zif268 protein-DNA complex refined at 1.6 A: a model system for understanding zinc finger-DNA interactions.. Elrod-Erickson M, Rould MA, Nekludova L, Pabo CO Structure 4 1171-80 (1996)
  2. Zinc finger phage: affinity selection of fingers with new DNA-binding specificities.. Rebar EJ, Pabo CO Science 263 671-3 (1994)
  3. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A.. Pavletich NP, Pabo CO Science 252 809-17 (1991)

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