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 language | English (US) |
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Pages (from-to) | 405-421 |
Number of pages | 17 |
Journal | Journal of Molecular Biology |
Volume | 363 |
Issue number | 2 |
DOIs | |
State | Published - Oct 20 2006 |
Keywords
- Aart
- peptide
- structure
- zinc finger
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology