Structure of Aart, a Designed Six-finger Zinc Finger Peptide, Bound to DNA

Structure of Aart, a Designed Six-finger Zinc Finger Peptide, Bound to DNA Cys2-His2 zinc fingers are one of the most common types of DNA-binding domains. Modifications to zinc-finger binding specificity have recently enabled custom DNA-binding proteins to be designed to a wide array of target sequences. We present here a 1.96 Å structure of Aart, a designed six-zinc finger protein, bound to a consensus DNA target site. This is the first structure of a designed protein with six fingers, and was intended to provide insights into the unusual affinity and specificity characteristics of this protein. Most protein−DNA contacts were found to be consistent with expectations, while others were unanticipated or insufficient to explain specificity. Several were unexpectedly mediated by glycerol, water molecules or amino acid−base stacking interactions. These results challenge some conventional concepts of recognition, particularly the finding that triplets containing 5′A, C, or T are typically not specified by direct interaction with the amino acid in position 6 of the recognition helix. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Biology Elsevier

Structure of Aart, a Designed Six-finger Zinc Finger Peptide, Bound to DNA

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Publisher
Elsevier
Copyright
Copyright © 2006 Elsevier Ltd
ISSN
0022-2836
D.O.I.
10.1016/j.jmb.2006.08.016
Publisher site
See Article on Publisher Site

Abstract

Cys2-His2 zinc fingers are one of the most common types of DNA-binding domains. Modifications to zinc-finger binding specificity have recently enabled custom DNA-binding proteins to be designed to a wide array of target sequences. We present here a 1.96 Å structure of Aart, a designed six-zinc finger protein, bound to a consensus DNA target site. This is the first structure of a designed protein with six fingers, and was intended to provide insights into the unusual affinity and specificity characteristics of this protein. Most protein−DNA contacts were found to be consistent with expectations, while others were unanticipated or insufficient to explain specificity. Several were unexpectedly mediated by glycerol, water molecules or amino acid−base stacking interactions. These results challenge some conventional concepts of recognition, particularly the finding that triplets containing 5′A, C, or T are typically not specified by direct interaction with the amino acid in position 6 of the recognition helix.

Journal

Journal of Molecular BiologyElsevier

Published: Oct 20, 2006

References

  • Efficient gene targeting in Drosophila with zinc finger nucleases
    Beumer, K.; Bhattacharyya, G.; Bibikova, M.; Trautman, J.K.; Carroll, D.
  • Geometric analysis and comparison of protein-DNA interfaces: why is there no simple code for recognition?
    Pabo, C.O.; Nekludova, L.
  • Crystallization and preliminary X-ray crystallographic analysis of Aart, a designed six-finger zinc-finger peptide, bound to DNA
    Crotty, J.W.; Etzkorn, C.; Barbas, C.F.; Segal, D.J.; Horton, N.C.
  • Automated MAD and MIR structure solution
    Terwilliger, T.C.; Berendzen, J.
  • Crystallography & NMR system: a new software suite for macromolecular structure determination
    Brünger, A.T.; Adams, P.D.; Clore, G.M.; DeLano, W.L.; Gros, P.; Grosse-Kunstleve, R.W.
  • Analysis of zinc fingers optimized via phage display: evaluating the utility of a recognition code
    Wolfe, S.A.; Greisman, H.A.; Ramm, E.I.; Pabo, C.O.
  • Constraints for zinc finger linker design as inferred from X-ray crystal structure of tandem Zif268-DNA complexes
    Peisach, E.; Pabo, C.O.
  • Effects of different zinc finger transcription factors on genomic targets
    Neuteboom, L.W.; Lindhout, B.I.; Saman, I.L.; Hooykaas, P.J.; van der Zaal, B.J.

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