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Structure and Function of the CBP/p300 TAZ Domains

  • Chapter
Zinc Finger Proteins

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

The TAZ (transcriptional adapter zinc binding) domains in the transcriptional coactivators CBP/p300 are zinc-binding motifs that are primarily involved in protein-protein recognition. The activation domains of more than 30 transcription factors have been reported to bind to the TAZ domains, and each TAZ domain generally binds a different subset of transcription factors. Structurally, the TAZ domains contain three zinc binding sites and four alpha helices that are packed against each other to form a hydrophobic core. Each zinc atom is bound to one histidine and three cysteine residues that are located at the end of one helix, in the interconnecting loop, and at the beginning of a second helix, forming a characteristic HCCC-type zinc binding motif. In the absence of zinc, the proteins are unfolded. The role of the zinc atoms is to organize and stabilize the four amphipathic helices into a global fold, which then serves as the site of protein-protein interaction. The TAZ1 domains of CBP and p300 binds other proteins mostly by hydrophobic interactions in the grooves and canyons created by the helical interfaces. The first three helices of TAZ1 and TAZ2 are structurally homologous; the fourth helix, however, is in a different relative orientation. This major structural difference between the two domains appears to play an important role in determining the protein-binding specificity of the TAZ domain.

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Authors and Affiliations

  1. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA

    Roberto N. De Guzman, Maria A. Martinez-Yamout, H. Jane Dyson & Peter E. Wright

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  1. Roberto N. De Guzman
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  2. Maria A. Martinez-Yamout
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  3. H. Jane Dyson
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  4. Peter E. Wright
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Correspondence to Peter E. Wright .

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  1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Shiro Iuchi

  2. Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Natalie Kuldell

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De Guzman, R.N., Martinez-Yamout, M.A., Dyson, H.J., Wright, P.E. (2005). Structure and Function of the CBP/p300 TAZ Domains. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_17

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