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
Hauptverfasser: Wanyun Sheng, Hong Yan, Francisco M. Rausa III, Robert H. Costa, Xiubei Liao
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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M403805200