Abstract
The region responsible for sequence-specific DNA binding by the transcription factor ADR1 contains two Cys2–His2 zinc fingers and an additional N-terminal proximal accessory region (PAR). The N-terminal (non-finger) PAR is unstructured in the absence of DNA and undergoes a folding transition on binding the DNA transcription target site. We have used a set of HN-HN NOEs derived from a perdeuterated protein–DNA complex to describe the fold of ADR1 bound to the UAS1 binding site. The PAR forms a compact domain consisting of three antiparallel strands that contact A-T base pairs in the major groove. The three-strand domain is a novel fold among all known DNA-binding proteins. The PAR shares sequence homology with the N-terminal regions of other zinc finger proteins, suggesting that it represents a new DNA-binding module that extends the binding repertoire of zinc finger proteins.
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Acknowledgements
We thank E.T. Young and C. Rohl for their helpful comments and suggestions in preparing this manuscript. We thank P. Rajagopal for the generous help with NMR experiment implementation and data collection. This work was supported by a grant from the National Institutes of Health. P.M.B. (Department of Biochemistry) was supported by a Public Health Service National Research Award from the National Institute of General Medical Sciences. L.E.S. (Molecular and Cellular Biology Program) was supported by a NIH predoctoral traineeship in Molecular Biophysics.
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Bowers, P., Schaufler, L. & Klevit, R. A folding transition and novel zinc finger accessory domain in the transcription factor ADR1. Nat Struct Mol Biol 6, 478–485 (1999). https://doi.org/10.1038/8283
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DOI: https://doi.org/10.1038/8283
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