Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA
Autor: | Xiubei Liao, Wanyun Sheng, Robert H. Costa, Hong Yan, Francisco M. Rausa |
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Rok vydání: | 2004 |
Předmět: |
Models
Molecular Protein Folding Magnetic Resonance Spectroscopy Protein family Protein domain Molecular Sequence Data Sequence Homology Biology digestive system Biochemistry chemistry.chemical_compound Mice EVH1 domain Acetyltransferases Animals Amino Acid Sequence Hepatocyte Nuclear Factor 1-alpha Cyclic AMP Response Element-Binding Protein Molecular Biology Histone Acetyltransferases Homeodomain Proteins Binding Sites POU domain Molecular Structure C-terminus Nuclear Proteins Cell Biology DNA-binding domain DNA Molecular biology DNA-Binding Proteins Solutions Hepatocyte Nuclear Factor 6 chemistry embryonic structures Hepatocyte Nuclear Factor 1 Biophysics Trans-Activators Octamer Transcription Factor-6 Alpha helix Transcription Factors |
Zdroj: | The Journal of biological chemistry. 279(32) |
ISSN: | 0021-9258 |
Popis: | Hepatocyte nuclear factor 6 (HNF-6) belongs to the family of One Cut transcription factors (also known as OC-1) and is essential for the development of the mouse pancreas, gall bladder, and the interhepatic bile ducts. HNF-6 binds to DNA as a monomer utilizing a single cut domain and a divergent homeodomain motif located at its C terminus. Here, we have used NMR methods to determine the solution structures of the 162 amino acid residue DNA-binding domain of the HNF-6alpha protein. The resulting overall structure of HNF-6alpha has two different distinct domains: the Cut domain and the Homeodomain connected by a long flexible linker. Our NMR structure shows that the Cut domain folds into a topology homologous to the POU DNA-binding domain, even though the sequences of these two protein families do not show homology. The DNA contact sequence of the HNF-6alpha was mapped with chemical shift perturbation methods. Our data also show that a proposed CREB-binding protein histone acetyltransferase protein-recruiting sequence, LSDLL, forms a helix and is involved in the hydrophobic core of the Cut domain. The structure implies that this sequence has to undergo structural changes when it interacts with CREB-binding protein. |
Databáze: | OpenAIRE |
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