CBP/p300 TAZ1 Domain Forms a Structured Scaffold for Ligand Binding
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- 作者：Roberto N. De Guzman ; Jonathan M. Wojciak ; Maria A. Martinez-Yamout ; H. Jane Dyson ; and Peter E. Wright
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：January 18, 2005
- 年：2005
- 卷：44
- 期：2
- 页码：490 - 497
- 全文大小：675K
- 年卷期：v.44,no.2(January 18, 2005)
- ISSN：1520-4995
文摘
The transcriptional coactivator protein CBP and its paralog p300 each contain two homologouszinc-containing TAZ domains, which constitute the interaction sites for a number of transcription factors.Previous reports of the three-dimensional structures of TAZ1 in complex with binding partners and of theisolated CBP TAZ2 domain show a distinctive topology composed of four amphipathic helices, organizedby three zinc-binding clusters with HCCC-type coordination. The isolated CBP TAZ2 domain forms astable three-dimensional structure in solution, but a recent report [Dial, R., Sun, Z., and Freedman, S. J.(2003) Biochemistry 42, 9937] suggested that the isolated p300 TAZ1 domain lacks a well-defined structureand behaves like a molten globule, even in the presence of Zn2+, and that the formation of a stable three-dimensional structure requires binding of a protein partner. In marked contrast to this result, we find thatboth the CBP and p300 TAZ domains in the presence of stoichiometric concentrations of Zn2+ adopt awell-defined structure in solution in the absence of binding partners. We have determined the three-dimensional structure of the isolated CBP TAZ1 domain by NMR methods and show that it has the samestructure in the presence and absence of binding partners. This is an important finding: whether the freeTAZ1 domain forms a folded structure or behaves as a molten globule will have a significant bearing onthe mechanism of protein-protein recognition. Although TAZ1 and TAZ2 share many structural similarities,there is a major structural difference: the fourth helix is oriented in opposite directions in the TAZ1 andTAZ2 domains. The structure of the free TAZ1 domain suggests that this difference is an inherent featurethat determines binding specificity and facilitates discrimination between different subsets of transcriptionfactors by the two TAZ domains.