Structure of the Hepatocyte Nuclear Factor 6α and Its Interaction with DNA
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 hom...
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Veröffentlicht in: | The Journal of biological chemistry 2004-08, Vol.279 (32), p.33928 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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-6α protein. The resulting
overall structure of HNF-6α 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-6α 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M403805200 |