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21 Solution Structures of DNA-binding Domains of Eukaryotic Transcription Factors

Peter E. Wright


The modular architecture of transcription factors frequently allows isolation of small domains suitable for structural determination by nuclear magnetic resonance (NMR) methods. NMR has played a major role in structural characterization of zinc-containing DNA-binding domains. Three-dimensional structures have been determined for classic TFIIIA-like zinc fingers (C2H2 zinc fingers), for nuclear receptor DNA-binding domains (C2C2 zinc fingers), and for the zinc-binding motif of a retroviral single-stranded nucleic-acid-binding protein (C2HC zinc finger). In the C2H2 and C2C2 zinc finger domains, the zinc plays an important role in stabilization of a helix for sequence-specific interaction with the major groove of DNA. In contrast, the basic region of the leucine-zipper-type DNA-binding motif is predominantly unfolded in the free protein and forms a stable helix only upon formation of a specific complex with DNA.

In recent years, multidimensional NMR spectroscopy has developed into a powerful technique for determining the three-dimensional structures of proteins in solution. Although intact transcription factors are too large for direct NMR studies, their modular architecture frequently allows isolation of small domains suitable for structure determination by NMR methods (for a brief discussion of the principles and methodology of NMR spectroscopy, see Wüthrich and Gehring, this volume). Much of our knowledge of the three-dimensional structures of eukaryotic transcription factors came originally from NMR spectroscopy. These structures and their functional implications are reviewed in this chapter, with particular emphasis on zinc-containing DNA-binding domains and the dimerization and DNA-binding domains of leucine zipper transcription factors. NMR structures of the Antennapedia homeodomain, which...

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