Abstract
Homeodomains are one of the key families of eukaryotic DNA-binding motifs and provide an important model system for studying protein–DNA interactions. We have crystallized the Antennapedia homeodomain–DNA complex and solved this structure at 2.4 Å resolution. NMR and molecular dynamics studies had implied that this homeodomain achieves specificity through an ensemble of rapidly fluctuating DNA contacts. The crystal structure is in agreement with the underlying NMR data, but our structure reveals a well-defined set of contacts and also reveals the locations and roles of water molecules at the protein–DNA interface. The synthesis of X-ray and NMR studies provides a unified, general model for homeodomain–DNA interactions.
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Acknowledgements
This work was supported by a National Institutes of Health grant to C.O.P. who is also in the Howard Hughes Medical Institute. Crystallographic data were collected with equipment purchased with support from the PEW Charitable Trusts and at the W. M. Keck Foundation X-ray Crystallography Facility at the Whitehead Institute (Cambridge, Massachusetts). We thank T. Benson, J. Hoch, P. Kim, M. Rould, M. Summers and S. Wolfe for helpful discussions; D. King for mass spectrometry analysis; and L. Nekludova for assistance in comparison of homeodomain structures.
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Fraenkel, E., Pabo, C. Comparison of X-ray and NMR structures for the Antennapedia homeodomain–DNA complex. Nat Struct Mol Biol 5, 692–697 (1998). https://doi.org/10.1038/1382
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DOI: https://doi.org/10.1038/1382
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