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PDBsum entry 1s7e
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Transcription
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PDB id
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1s7e
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References listed in PDB file
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Key reference
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Title
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Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA.
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Authors
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W.Sheng,
H.Yan,
F.M.Rausa,
R.H.Costa,
X.Liao.
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Ref.
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J Biol Chem, 2004,
279,
33928-33936.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 2.
FIG. 2. Separation structures of Cut domain and Homeodomain
of HNF-6. A, best-fit superpositions of the 20 selected
conformers with the lowest target functions from the final DYANA
calculations colored as in Fig. 1. The Cut domain (red) and
Homeodomain (blue) are separately superimposed on the regular
secondary regions. B, ribbon backbone diagram of typical
structures of the Cut domain (red) and Homeodomain (blue) with
the lowest target functions.
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Figure 4.
FIG. 4. The structural comparison of the Cut homeodomain of
HNF-6 with the POU Homeodomain of Oct-1 (Protein Data Bank
accession number 1e3o [PDB]
) (for review see Ref. 36). A, backbone stereotrace of the
superposition of the Cut domain of HNF-6 with POU domain
obtained from NMR structure. The Cut domain of HNF-6 is colored
by red, and the POU domain is in green. B, the primary sequence
and secondary structure alignment of the Cut domain and the POU
domain. The conserved hydrophobic residues in the two domains
are highlighted with yellow color. C, the Homeodomain of HNF-6
with homeodomain of Oct-1 obtained from x-ray crystal structure.
Homeodomain of HNF-6 is colored by blue, and homeodomain of
Oct-1 is in green. D, the primary sequence and secondary
structure alignment of the two Homeodomains. The conserved
hydrophobic residues in the two domains are highlighted with
yellow color. Two unusual amino acid residues (Phe^147 and
Met149) in the Homeodomain of HNF-6 are indicated with an
asterisk.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
33928-33936)
copyright 2004.
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