Abstract
THAP-family C2CH zinc-coordinating DNA-binding proteins function in diverse eukaryotic cellular processes, such as transposition, transcriptional repression, stem-cell pluripotency, angiogenesis and neurological function. To determine the molecular basis for sequence-specific DNA recognition by THAP proteins, we solved the crystal structure of the Drosophila melanogaster P element transposase THAP domain (DmTHAP) in complex with a natural 10-base-pair site. In contrast to C2H2 zinc fingers, DmTHAP docks a conserved β-sheet into the major groove and a basic C-terminal loop into the adjacent minor groove. We confirmed specific protein-DNA interactions by mutagenesis and DNA-binding assays. Sequence analysis of natural and in vitro–selected binding sites suggests that several THAPs (DmTHAP and human THAP1 and THAP9) recognize a bipartite TXXGGGX(A/T) consensus motif; homology suggests THAP proteins bind DNA through a bipartite interaction. These findings reveal the conserved mechanisms by which THAP-family proteins engage specific chromosomal target elements.
Original language | English (US) |
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Pages (from-to) | 117-124 |
Number of pages | 8 |
Journal | Nature Structural and Molecular Biology |
Volume | 17 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2010 |
Externally published | Yes |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology