NMR Relaxation Study of the Complex Formed Between CBP and the Activation Domain of the Nuclear Hormone Receptor Coactivator ACTR
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- 作者：Marc-Olivier Ebert ; Sung-Hun Bae ; H. Jane Dyson ; Peter E. Wright
- 刊名：Biochemistry
- 出版年：2008
- 出版时间：February 5, 2008
- 年：2008
- 卷：47
- 期：5
- 页码：1299 - 1308
- 全文大小：661K
- 年卷期：v.47,no.5(February 5, 2008)
- ISSN：1520-4995
文摘
Overexpression of the p160 steroid receptor coactivator ACTR is associated with breast andovarian cancers. Complex formation between ACTR and the general transcriptional coactivators CBPand p300 plays a key role in the nuclear receptor-dependent regulation of gene transcription and was thefirst reported example of mutual synergistic folding of two disordered polypeptide chains. In order toinvestigate the structure and dynamics of the free domains and complex, we measured and analyzed 15Nlongitudinal and transverse relaxation rates and [1H]-15N heteronuclear Overhauser effects of the backboneamides of the free and bound forms of human ACTR (residues 1041-1088) and mouse CBP (residues2059-2117). Secondary chemical shifts for the free and bound forms were well correlated with the extentof backbone flexibility. The free ACTR domain has no residual secondary structure and shows all of thecharacteristics of a completely unfolded polypeptide chain. The free CBP domain retains most of the
-helical content seen in the complex but is significantly more flexible. Despite the disordered nature ofthe free individual domains, the complex has the motional characteristics of a completely folded proteincomplex and has no significant residual backbone fluctuation that might compensate for the massive lossof conformational entropy upon complex formation.
-helical content seen in the complex but is significantly more flexible. Despite the disordered nature ofthe free individual domains, the complex has the motional characteristics of a completely folded proteincomplex and has no significant residual backbone fluctuation that might compensate for the massive lossof conformational entropy upon complex formation.