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PDBsum entry 1yvl
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Signaling protein
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PDB id
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1yvl
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Structure of unphosphorylated stat1
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Structure:
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Signal transducer and activator of transcription 1- alpha/beta. Chain: a, b. Fragment: residues 1-683. Synonym: transcription factor isgf-3 components p91/p84. Engineered: yes. 5-residue peptide. Chain: c, d. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: stat1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized, the sequence is derived from human interferon gamma receptor alpha chain
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Biol. unit:
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Tetramer (from
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Resolution:
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3.00Å
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R-factor:
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0.240
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R-free:
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0.281
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Authors:
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X.Mao,Z.Ren,G.N.Parker,H.Sondermann,M.A.Pastorello,W.Wang, J.S.Mcmurray,B.Demeler,J.E.Darnell Jr.,X.Chen
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Key ref:
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X.Mao
et al.
(2005).
Structural bases of unphosphorylated STAT1 association and receptor binding.
Mol Cell,
17,
761-771.
PubMed id:
DOI:
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Date:
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16-Feb-05
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Release date:
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22-Mar-05
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PROCHECK
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Headers
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References
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P42224
(STAT1_HUMAN) -
Signal transducer and activator of transcription 1-alpha/beta from Homo sapiens
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Seq:
Struc:
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750 a.a.
652 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Mol Cell
17:761-771
(2005)
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PubMed id:
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Structural bases of unphosphorylated STAT1 association and receptor binding.
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X.Mao,
Z.Ren,
G.N.Parker,
H.Sondermann,
M.A.Pastorello,
W.Wang,
J.S.McMurray,
B.Demeler,
J.E.Darnell,
X.Chen.
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ABSTRACT
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The crystal structure has been determined at 3.0 A resolution for an
unphosphorylated STAT1 (1-683) complexed with a phosphopeptide derived from the
alpha chain of interferon gamma (IFNgamma) receptor. Two dimer interfaces are
seen, one between the N domains (NDs) (amino acid residues 1-123) and the other
between the core fragments (CFs) (residues 132-683). Analyses of the wild-type
(wt) and mutant STAT1 proteins by static light scattering, analytical
ultracentrifugation, and coimmunoprecipitation suggest that STAT1 is
predominantly dimeric prior to activation, and the dimer is mediated by the ND
interactions. The connecting region between the ND and the CF is flexible and
allows two interconvertable orientations of the CFs, termed
"antiparallel" or "parallel," as determined by SH2 domain
orientations. Functional implications of these dimer conformations are
discussed. Also revealed in this structure is the detailed interaction between
STAT1 SH2 domain and its docking site on IFNgamma receptor.
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Selected figure(s)
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Figure 1.
Figure 1. Structures of STAT1
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Figure 2.
Figure 2. Illustration of the Two Dimer Interfaces
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
17,
761-771)
copyright 2005.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.Wang,
Y.Yang,
N.Sharma,
N.I.Tarasova,
O.A.Timofeeva,
R.T.Winkler-Pickett,
S.Tanigawa,
and
A.O.Perantoni
(2010).
STAT1 activation regulates proliferation and differentiation of renal progenitors.
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Cell Signal,
22,
1717-1726.
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J.D.Nardozzi,
K.Lott,
and
G.Cingolani
(2010).
Phosphorylation meets nuclear import: a review.
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Cell Commun Signal,
8,
32.
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L.Ma,
J.S.Gao,
Y.Guan,
X.Shi,
H.Zhang,
M.K.Ayrapetov,
Z.Zhang,
L.Xu,
Y.M.Hyun,
M.Kim,
S.Zhuang,
and
Y.E.Chin
(2010).
Acetylation modulates prolactin receptor dimerization.
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Proc Natl Acad Sci U S A,
107,
19314-19319.
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N.H.Rosas-Murrieta,
I.Herrera-Camacho,
H.Palma-Ocampo,
G.Santos-López,
and
J.Reyes-Leyva
(2010).
Interaction of mumps virus V protein variants with STAT1-STAT2 heterodimer: experimental and theoretical studies.
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Virol J,
7,
263.
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X.F.Kong,
M.Ciancanelli,
S.Al-Hajjar,
L.Alsina,
T.Zumwalt,
J.Bustamante,
J.Feinberg,
M.Audry,
C.Prando,
V.Bryant,
A.Kreins,
D.Bogunovic,
R.Halwani,
X.X.Zhang,
L.Abel,
D.Chaussabel,
S.Al-Muhsen,
J.L.Casanova,
and
S.Boisson-Dupuis
(2010).
A novel form of human STAT1 deficiency impairing early but not late responses to interferons.
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Blood,
116,
5895-5906.
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Y.Zhang,
M.B.Cheng,
Y.J.Zhang,
X.Zhong,
H.Dai,
L.Yan,
N.H.Wu,
Y.Zhang,
and
Y.F.Shen
(2010).
A switch from hBrm to Brg1 at IFNγ-activated sequences mediates the activation of human genes.
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Cell Res,
20,
1345-1360.
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A.Chapgier,
X.F.Kong,
S.Boisson-Dupuis,
E.Jouanguy,
D.Averbuch,
J.Feinberg,
S.Y.Zhang,
J.Bustamante,
G.Vogt,
J.Lejeune,
E.Mayola,
L.de Beaucoudrey,
L.Abel,
D.Engelhard,
and
J.L.Casanova
(2009).
A partial form of recessive STAT1 deficiency in humans.
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J Clin Invest,
119,
1502-1514.
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C.E.Egwuagu
(2009).
STAT3 in CD4+ T helper cell differentiation and inflammatory diseases.
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Cytokine,
47,
149-156.
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O.H.Krämer,
S.K.Knauer,
G.Greiner,
E.Jandt,
S.Reichardt,
K.H.Gührs,
R.H.Stauber,
F.D.Böhmer,
and
T.Heinzel
(2009).
A phosphorylation-acetylation switch regulates STAT1 signaling.
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Genes Dev,
23,
223-235.
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P.Bernadó,
Y.Pérez,
J.Blobel,
J.Fernández-Recio,
D.I.Svergun,
and
M.Pons
(2009).
Structural characterization of unphosphorylated STAT5a oligomerization equilibrium in solution by small-angle X-ray scattering.
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Protein Sci,
18,
716-726.
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P.K.Mandal,
D.Limbrick,
D.R.Coleman,
G.A.Dyer,
Z.Ren,
J.S.Birtwistle,
C.Xiong,
X.Chen,
J.M.Briggs,
and
J.S.McMurray
(2009).
Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling.
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J Med Chem,
52,
2429-2442.
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T.M.Bernaciak,
J.Zareno,
J.T.Parsons,
and
C.M.Silva
(2009).
A novel role for signal transducer and activator of transcription 5b (STAT5b) in beta1-integrin-mediated human breast cancer cell migration.
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Breast Cancer Res,
11,
R52.
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W.Gan,
and
B.Roux
(2009).
Binding specificity of SH2 domains: insight from free energy simulations.
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Proteins,
74,
996.
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X.Hu,
and
L.B.Ivashkiv
(2009).
Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases.
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Immunity,
31,
539-550.
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X.Li,
M.Yu,
and
M.Zhu
(2009).
Innate immune signaling pathways in animals: beyond reductionism.
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Int Rev Immunol,
28,
207-238.
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X.Wang,
P.Lupardus,
S.L.Laporte,
and
K.C.Garcia
(2009).
Structural biology of shared cytokine receptors.
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Annu Rev Immunol,
27,
29-60.
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C.Schindler,
and
C.Plumlee
(2008).
Inteferons pen the JAK-STAT pathway.
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Semin Cell Dev Biol,
19,
311-318.
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F.Han,
Y.Luo,
N.Ge,
and
J.Xu
(2008).
Construction of fluorescence resonance energy transfer vectors and their application in study of structure and function of signal transducers and activators of transcription 1.
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Acta Biochim Biophys Sin (Shanghai),
40,
934-942.
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I.Lappalainen,
J.Thusberg,
B.Shen,
and
M.Vihinen
(2008).
Genome wide analysis of pathogenic SH2 domain mutations.
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Proteins,
72,
779-792.
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I.Sadzak,
M.Schiff,
I.Gattermeier,
R.Glinitzer,
I.Sauer,
A.Saalmüller,
E.Yang,
B.Schaljo,
and
P.Kovarik
(2008).
Recruitment of Stat1 to chromatin is required for interferon-induced serine phosphorylation of Stat1 transactivation domain.
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Proc Natl Acad Sci U S A,
105,
8944-8949.
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J.S.McMurray
(2008).
Structural basis for the binding of high affinity phosphopeptides to Stat3.
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Biopolymers,
90,
69-79.
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J.W.Kornfeld,
F.Grebien,
M.A.Kerenyi,
K.Friedbichler,
B.Kovacic,
B.Zankl,
A.Hoelbl,
H.Nivarti,
H.Beug,
V.Sexl,
M.Muller,
L.Kenner,
E.W.Mullner,
F.Gouilleux,
and
R.Moriggl
(2008).
The different functions of Stat5 and chromatin alteration through Stat5 proteins.
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Front Biosci,
13,
6237-6254.
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N.Wenta,
H.Strauss,
S.Meyer,
and
U.Vinkemeier
(2008).
Tyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations.
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Proc Natl Acad Sci U S A,
105,
9238-9243.
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P.B.Sehgal
(2008).
Paradigm shifts in the cell biology of STAT signaling.
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Semin Cell Dev Biol,
19,
329-340.
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T.Hou,
S.Ray,
C.Lee,
and
A.R.Brasier
(2008).
The STAT3 NH2-terminal Domain Stabilizes Enhanceosome Assembly by Interacting with the p300 Bromodomain.
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J Biol Chem,
283,
30725-30734.
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A.N.Bullock,
M.C.Rodriguez,
J.E.Debreczeni,
Z.Songyang,
and
S.Knapp
(2007).
Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation.
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Structure,
15,
1493-1504.
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PDB code:
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B.Barré,
A.Vigneron,
N.Perkins,
I.B.Roninson,
E.Gamelin,
and
O.Coqueret
(2007).
The STAT3 oncogene as a predictive marker of drug resistance.
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Trends Mol Med,
13,
4.
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B.R.Tenoever,
S.L.Ng,
M.A.Chua,
S.M.McWhirter,
A.García-Sastre,
and
T.Maniatis
(2007).
Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity.
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Science,
315,
1274-1278.
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C.D.Krause,
and
S.Pestka
(2007).
Historical developments in the research of interferon receptors.
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Cytokine Growth Factor Rev,
18,
473-482.
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M.Andrianifahanana,
A.P.Singh,
C.Nemos,
M.P.Ponnusamy,
N.Moniaux,
P.P.Mehta,
G.C.Varshney,
and
S.K.Batra
(2007).
IFN-gamma-induced expression of MUC4 in pancreatic cancer cells is mediated by STAT-1 upregulation: a novel mechanism for IFN-gamma response.
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Oncogene,
26,
7251-7261.
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N.C.Reich
(2007).
STAT dynamics.
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Cytokine Growth Factor Rev,
18,
511-518.
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Q.Zhu,
and
N.Jing
(2007).
Computational study on mechanism of G-quartet oligonucleotide T40214 selectively targeting Stat3.
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J Comput Aided Mol Des,
21,
641-648.
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R.G.Rosenfeld,
A.Belgorosky,
C.Camacho-Hubner,
M.O.Savage,
J.M.Wit,
and
V.Hwa
(2007).
Defects in growth hormone receptor signaling.
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Trends Endocrinol Metab,
18,
134-141.
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S.Unlu,
A.Kumar,
W.R.Waterman,
J.Tsukada,
K.Z.Wang,
D.L.Galson,
and
P.E.Auron
(2007).
Phosphorylation of IRF8 in a pre-associated complex with Spi-1/PU.1 and non-phosphorylated Stat1 is critical for LPS induction of the IL1B gene.
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Mol Immunol,
44,
3364-3379.
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T.Meyer,
and
U.Vinkemeier
(2007).
STAT nuclear translocation: potential for pharmacological intervention.
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Expert Opin Ther Targets,
11,
1355-1365.
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A.Chapgier,
S.Boisson-Dupuis,
E.Jouanguy,
G.Vogt,
J.Feinberg,
A.Prochnicka-Chalufour,
A.Casrouge,
K.Yang,
C.Soudais,
C.Fieschi,
O.F.Santos,
J.Bustamante,
C.Picard,
L.de Beaucoudrey,
J.F.Emile,
P.D.Arkwright,
R.D.Schreiber,
C.Rolinck-Werninghaus,
A.Rösen-Wolff,
K.Magdorf,
J.Roesler,
and
J.L.Casanova
(2006).
Novel STAT1 alleles in otherwise healthy patients with mycobacterial disease.
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PLoS Genet,
2,
e131.
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C.D.Krause,
N.Lavnikova,
J.Xie,
E.Mei,
O.V.Mirochnitchenko,
Y.Jia,
R.M.Hochstrasser,
and
S.Pestka
(2006).
Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains.
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Cell Res,
16,
55-69.
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C.Mertens,
M.Zhong,
R.Krishnaraj,
W.Zou,
X.Chen,
and
J.E.Darnell
(2006).
Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain.
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Genes Dev,
20,
3372-3381.
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C.P.Lim,
and
X.Cao
(2006).
Structure, function, and regulation of STAT proteins.
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Mol Biosyst,
2,
536-550.
|
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K.Crozat,
P.Georgel,
S.Rutschmann,
N.Mann,
X.Du,
K.Hoebe,
and
B.Beutler
(2006).
Analysis of the MCMV resistome by ENU mutagenesis.
|
| |
Mamm Genome,
17,
398-406.
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L.Li,
and
P.E.Shaw
(2006).
Elevated activity of STAT3C due to higher DNA binding affinity of phosphotyrosine dimer rather than covalent dimer formation.
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J Biol Chem,
281,
33172-33181.
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L.Zhang,
D.B.Badgwell,
J.J.Bevers,
K.Schlessinger,
P.J.Murray,
D.E.Levy,
and
S.S.Watowich
(2006).
IL-6 signaling via the STAT3/SOCS3 pathway: functional analysis of the conserved STAT3 N-domain.
|
| |
Mol Cell Biochem,
288,
179-189.
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M.Shah,
K.Patel,
S.Mukhopadhyay,
F.Xu,
G.Guo,
and
P.B.Sehgal
(2006).
Membrane-associated STAT3 and PY-STAT3 in the cytoplasm.
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| |
J Biol Chem,
281,
7302-7308.
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N.C.Reich,
and
L.Liu
(2006).
Tracking STAT nuclear traffic.
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Nat Rev Immunol,
6,
602-612.
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A.Prabhu,
E.Coutinho,
and
S.Srivastava
(2005).
The amino-terminal domain of human signal transducers and activators of transcription 1: overexpression, purification and characterization.
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J Biosci,
30,
611-618.
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C.M.Ulane,
A.Kentsis,
C.D.Cruz,
J.P.Parisien,
K.L.Schneider,
and
C.M.Horvath
(2005).
Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain.
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J Virol,
79,
10180-10189.
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D.Neculai,
A.M.Neculai,
S.Verrier,
K.Straub,
K.Klumpp,
E.Pfitzner,
and
S.Becker
(2005).
Structure of the unphosphorylated STAT5a dimer.
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| |
J Biol Chem,
280,
40782-40787.
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PDB code:
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L.Liu,
K.M.McBride,
and
N.C.Reich
(2005).
STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3.
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| |
Proc Natl Acad Sci U S A,
102,
8150-8155.
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X.Mao,
and
X.Chen
(2005).
Crystallization and X-ray crystallographic analysis of human STAT1.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
61,
666-668.
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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.
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Links
