Structure of the hepatocyte nuclear factor 6alpha 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 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.
Sheng
Wanyun
W
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Yan
Hong
H
Rausa
Francisco M
FM
Costa
Robert H
RH
Liao
Xiubei
X
D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051559:Hepatocyte Nuclear Factor 6; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009687:Nuclear Proteins; D050816:Octamer Transcription Factor-6; D017510:Protein Folding; D017385:Sequence Homology; D012996:Solutions; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D051559:Hepatocyte Nuclear Factor 6; C496488:Hnf1a protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C496606:Onecut1 protein, mouse; C494180:Pou3f1 protein, mouse; D012996:Solutions; D015534:Trans-Activators; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D050816:Octamer Transcription Factor-6; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases