 |
PDBsum entry 2hfh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hnf-3 homologues
|
PDB id
|
|
|
|
2hfh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Mol Biol
278:293-299
(1998)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural changes in the region directly adjacent to the DNA-binding helix highlight a possible mechanism to explain the observed changes in the sequence-specific binding of winged helix proteins.
|
|
I.Marsden,
C.Jin,
X.Liao.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The hepatocyte nuclear factor 3 (HNF-3)/fork head (fkh) family contains a large
number of transcription factors and folds into a winged helix motif. Despite
having almost invariable amino acid sequences in their principal DNA-binding
helices, HNF-3/fkh proteins show a wide diversity of sequence-specific binding.
Previous studies of chimeric HNF-3/fkh proteins demonstrated that the binding
specificity is primarily influenced by a region directly adjacent to the binding
helix. We report our findings of an NMR structural study performed on an
HNF-3/fkh family member (Genesis, formerly HFH-2) and compare it to that of
another family member (HNF-3gamma) complexed to DNA and determined by X-ray
crystallography. It is found that in comparison to HNF-3gamma, Genesis contains
an extra small helix directly prior to the N terminus of the primary DNA contact
helix. Due to the insertion of this helix, a shorter and slightly re-positioned
primary DNA contact helix is observed, which we believe leads to the DNA-binding
specificity differences among family members.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 2.
Figure 2. A stereo diagram showing the superposition of the
20 best calculated DIANA structures of Genesis.
|
|
Figure 3.
Figure 3. A, A ribbon diagram showing the NMR-derived
tertiary structure of Genesis. B, A ribbon diagram showing the
X-ray crystal structure of HNF-3γ [Clark et al 1993]. C, A
stereo diagram of the backbone C^α atom coordinates of the core
helices of Genesis (green) overlaid with those of HNF-3γ (red).
Diagrams were produced with MOLMOL, a molecular graphics program
for displaying and analyzing the 3D structures of biological
molecules [Koradi et al 1996].
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
278,
293-299)
copyright 1998.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
Y.P.Chu,
C.H.Chang,
J.H.Shiu,
Y.T.Chang,
C.Y.Chen,
and
W.J.Chuang
(2011).
Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping and DNA binding.
|
| |
Protein Sci,
20,
908-924.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
D.R.Littler,
M.Alvarez-Fernández,
A.Stein,
R.G.Hibbert,
T.Heidebrecht,
P.Aloy,
R.H.Medema,
and
A.Perrakis
(2010).
Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence.
|
| |
Nucleic Acids Res,
38,
4527-4538.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
S.Nakamura,
I.Hirano,
K.Okinaka,
T.Takemura,
D.Yokota,
T.Ono,
K.Shigeno,
K.Shibata,
S.Fujisawa,
and
K.Ohnishi
(2010).
The FOXM1 transcriptional factor promotes the proliferation of leukemia cells through modulation of cell cycle progression in acute myeloid leukemia.
|
| |
Carcinogenesis,
31,
2012-2021.
|
|
|
|
|
|
|
L.M.Xia,
W.J.Huang,
B.Wang,
M.Liu,
Q.Zhang,
W.Yan,
Q.Zhu,
M.Luo,
Z.Z.Zhou,
and
D.A.Tian
(2009).
Transcriptional up-regulation of FoxM1 in response to hypoxia is mediated by HIF-1.
|
| |
J Cell Biochem,
106,
247-256.
|
|
|
|
|
|
|
C.D.Fetterman,
B.Rannala,
and
M.A.Walter
(2008).
Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies.
|
| |
BMC Evol Biol,
8,
261.
|
|
|
|
|
|
|
M.Nagaki,
and
H.Moriwaki
(2008).
Transcription factor HNF and hepatocyte differentiation.
|
| |
Hepatol Res,
38,
961-969.
|
|
|
|
|
|
|
T.Obsil,
and
V.Obsilova
(2008).
Structure/function relationships underlying regulation of FOXO transcription factors.
|
| |
Oncogene,
27,
2263-2275.
|
|
|
|
|
|
|
G.A.Gusarova,
I.C.Wang,
M.L.Major,
V.V.Kalinichenko,
T.Ackerson,
V.Petrovic,
and
R.H.Costa
(2007).
A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment.
|
| |
J Clin Invest,
117,
99.
|
|
|
|
|
|
|
K.L.Tsai,
C.Y.Huang,
C.H.Chang,
Y.J.Sun,
W.J.Chuang,
and
C.D.Hsiao
(2006).
Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins.
|
| |
J Biol Chem,
281,
17400-17409.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Y.Tan,
Y.Yoshida,
D.E.Hughes,
and
R.H.Costa
(2006).
Increased expression of hepatocyte nuclear factor 6 stimulates hepatocyte proliferation during mouse liver regeneration.
|
| |
Gastroenterology,
130,
1283-1300.
|
|
|
|
|
|
|
I.C.Wang,
Y.J.Chen,
D.Hughes,
V.Petrovic,
M.L.Major,
H.J.Park,
Y.Tan,
T.Ackerson,
and
R.H.Costa
(2005).
Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase.
|
| |
Mol Cell Biol,
25,
10875-10894.
|
|
|
|
|
|
|
R.H.Costa,
V.V.Kalinichenko,
M.L.Major,
and
P.Raychaudhuri
(2005).
New and unexpected: forkhead meets ARF.
|
| |
Curr Opin Genet Dev,
15,
42-48.
|
|
|
|
|
|
|
M.L.Major,
R.Lepe,
and
R.H.Costa
(2004).
Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators.
|
| |
Mol Cell Biol,
24,
2649-2661.
|
|
|
|
|
|
|
O.J.Lehmann,
J.C.Sowden,
P.Carlsson,
T.Jordan,
and
S.S.Bhattacharya
(2003).
Fox's in development and disease.
|
| |
Trends Genet,
19,
339-344.
|
|
|
|
|
|
|
V.V.Kalinichenko,
G.A.Gusarova,
Y.Tan,
I.C.Wang,
M.L.Major,
X.Wang,
H.M.Yoder,
R.H.Costa,
and
R.H.Costal
(2003).
Ubiquitous expression of the forkhead box M1B transgene accelerates proliferation of distinct pulmonary cell types following lung injury.
|
| |
J Biol Chem,
278,
37888-37894.
|
|
|
|
|
|
|
W.Sheng,
M.Rance,
and
X.Liao
(2002).
Structure comparison of two conserved HNF-3/fkh proteins HFH-1 and genesis indicates the existence of folding differences in their complexes with a DNA binding sequence.
|
| |
Biochemistry,
41,
3286-3293.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
A.N.Lane,
L.M.Hays,
N.Tsvetkova,
R.E.Feeney,
L.M.Crowe,
and
J.H.Crowe
(2000).
Comparison of the solution conformation and dynamics of antifreeze glycoproteins from Antarctic fish.
|
| |
Biophys J,
78,
3195-3207.
|
|
|
|
|
|
|
C.Pérez-Sánchez,
M.A.Gómez-Ferrería,
C.A.de La Fuente,
B.Granadino,
G.Velasco,
A.Esteban-Gamboa,
and
J.Rey-Campos
(2000).
FHX, a novel fork head factor with a dual DNA binding specificity.
|
| |
J Biol Chem,
275,
12909-12916.
|
|
|
|
|
|
|
F.M.Rausa,
Y.Tan,
H.Zhou,
K.W.Yoo,
D.B.Stolz,
S.C.Watkins,
R.R.Franks,
T.G.Unterman,
and
R.H.Costa
(2000).
Elevated levels of hepatocyte nuclear factor 3beta in mouse hepatocytes influence expression of genes involved in bile acid and glucose homeostasis.
|
| |
Mol Cell Biol,
20,
8264-8282.
|
|
|
|
|
|
|
K.S.Gajiwala,
and
S.K.Burley
(2000).
Winged helix proteins.
|
| |
Curr Opin Struct Biol,
10,
110-116.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
|
Links
