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PDBsum entry 1y1u
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Signaling protein
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PDB id
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1y1u
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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 unphosphorylated stat5a dimer.
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Authors
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D.Neculai,
A.M.Neculai,
S.Verrier,
K.Straub,
K.Klumpp,
E.Pfitzner,
S.Becker.
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Ref.
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J Biol Chem, 2005,
280,
40782-40787.
[DOI no: ]
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PubMed id
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Abstract
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STAT proteins have the function of signaling from the cell membrane into the
nucleus, where they regulate gene transcription. Latent mammalian STAT proteins
can form dimers in the cytoplasm even before receptor-mediated activation by
specific tyrosine phosphorylation. Here we describe the 3.21-A crystal structure
of an unphosphorylated STAT5a homodimer lacking the N-terminal domain as well as
the C-terminal transactivation domain. The overall structure of this fragment is
very similar to phosphorylated STATs. However, important differences exist in
the dimerization mode. Although the interface between phosphorylated STATs is
mediated by their Src-homology 2 domains, the unphosphorylated STAT5a fragment
dimerizes in a completely different manner via interactions between their
beta-barrel and four-helix bundle domains. The STAT4 N-terminal domain dimer can
be docked onto this STAT5a core fragment dimer based on shape and charge
complementarities. The separation of the dimeric arrangement, taking place upon
activation and nuclear translocation of STAT5a, is demonstrated by fluorescence
resonance energy transfer experiments in living cells.
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Figure 2.
FIGURE 2. The quality of the electron density allows the
identification of intermolecular contacts in the Stat5a dimer.
A, 2 mF[o] - DF[c] electron density map contoured at 2  level
around the 2-fold axis of the dimer. B, the residues involved in
the interactions at the interface are colored according to each
monomer after the color coding from Fig. 1B. For clarity only
some of them have been labeled. Hydrogen bonds are represented
as dashed lines.
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Figure 3.
FIGURE 3. Docking model of the N-terminal domain dimer
structure of STAT4 onto the dimeric STAT5a core fragment
assuming coincidence of their dyads. A, side view of the
ensemble. An arrow indicates the dyad. Dashed lines symbolize
the missing residues between the C termini of the N-terminal
domains and the N termini of the core domains. The color coding
for the STAT5a dimer is identical to the one used in Fig. 1A,
and the N-terminal domain dimer is colored in cyan. B,
electrostatic potential representations of matched surfaces of
the docking partners. The common 2-fold axis is indicated by an
X, and the complementary surfaces are encircled.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
40782-40787)
copyright 2005.
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