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

David J. Segal, Justin W. Crotty, Mital S. Bhakta, Carlos F. Barbas, Nancy C Horton

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)405-421
Number of pages17
JournalJournal of Molecular Biology
Volume363
Issue number2
DOIs
StatePublished - Oct 20 2006

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Zinc Fingers
Fingers
Peptides
DNA
Proteins
Amino Acids
DNA-Binding Proteins
Glycerol
Water

Keywords

  • Aart
  • peptide
  • structure
  • zinc finger

ASJC Scopus subject areas

  • Virology

Cite this

Structure of Aart, a Designed Six-finger Zinc Finger Peptide, Bound to DNA. / Segal, David J.; Crotty, Justin W.; Bhakta, Mital S.; Barbas, Carlos F.; Horton, Nancy C.

In: Journal of Molecular Biology, Vol. 363, No. 2, 20.10.2006, p. 405-421.

Research output: Contribution to journalArticle

Segal, David J. ; Crotty, Justin W. ; Bhakta, Mital S. ; Barbas, Carlos F. ; Horton, Nancy C. / Structure of Aart, a Designed Six-finger Zinc Finger Peptide, Bound to DNA. In: Journal of Molecular Biology. 2006 ; Vol. 363, No. 2. pp. 405-421.
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