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Structural diversity in p160/CREB-binding protein coactivator complexes.
Lorna Waters1, Baigong Yue, Vaclav Veverka
1Department of Biochemistry, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
The Journal of Biological Chemistry
|March 17, 2006
Summary
Nuclear receptor transcription relies on coactivators like SRC1 and CBP. We determined the structure of a CBP-SRC1 complex, revealing distinct domain topologies that likely confer functional specificity in coactivator complexes.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Nuclear receptors regulate gene transcription upon ligand binding.
- This process involves coactivator proteins, including p160 family members like SRC1.
- p160 coactivators interact with histone acetyltransferases such as CBP and p300.
Purpose of the Study:
- To elucidate the solution structure of the complex between the CBP SRC1 interaction domain (SID) and the SRC1 activation domain (AD1).
- To compare the structural organization of this complex with related coactivator complexes.
Main Methods:
- Solution structure determination using biophysical techniques.
- Analysis of protein-protein interactions within the CBP SID-SRC1 AD1 complex.
Main Results:
- A stable four-helix bundle is formed by specific helical regions of CBP SID and SRC1 AD1.
- The SRC1 AD1 domain exhibits a different topology compared to the related ACTR protein.
- Specific SRC1 helices (Salpha2' and Salpha2) are not directly involved in the interface but position other helices.
Conclusions:
- The CBP SID domain maintains a similar fold when interacting with different p160 proteins.
- The distinct topologies of AD1 domains contribute to the functional specificity of coactivator complexes.
- Understanding these structural differences is crucial for deciphering the mechanisms of gene regulation by nuclear receptors.