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PDBsum entry 1imh
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Transcription/DNA
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PDB id
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1imh
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Contents |
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* Residue conservation analysis
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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 a tonebp-Dna complex reveals DNA encircled by a transcription factor.
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Authors
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J.C.Stroud,
C.Lopez-Rodriguez,
A.Rao,
L.Chen.
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Ref.
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Nat Struct Biol, 2002,
9,
90-94.
[DOI no: ]
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PubMed id
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Abstract
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Tonicity-responsive enhancer binding protein (TonEBP), also known as NFAT5, is a
unique member of the NFAT family of transcription factors that regulates gene
expression induced by osmotic stress in mammalian cells. Unlike monomeric
members of the NFAT family, TonEBP exists as a homodimer and binds asymmetric
TonE DNA sites; furthermore, the affinity of TonEBP for DNA is much lower than
that of other NFAT proteins. How TonEBP recognizes the TonE site and regulates
the activation of hypertonicity response genes has not been clear. Here we show
that TonEBP adopts a NF-kappaB-like structure upon binding to DNA, providing a
direct structural link between the NFAT and NF-kappaB family of transcription
factors. We also show that TonEBP completely encircles its DNA target and
present biochemical evidence that the DNA encirclement may lead to increased
kinetic stability of the TonEBP-DNA complex. Thus, the list of proteins that
bind DNA by encirclement is now expanded to include sequence-specific
transcription factors.
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Figure 1.
Figure 1. Structure of the TonEBP -DNA complex. a, Overall
structure. The following scheme is used for all illustrations
except Fig. 3c: the N-terminal (RHR-N) and C-terminal (RHR-C)
domains of TonEBP are colored yellow and green, respectively.
Strands and helices are labeled; the lettering corresponds to
that used for NFAT1 (ref. 4). DNA is shown in the stick model.
The sequence of the DNA used in the crystals is shown below the
figure. b, Structure-based sequence alignment of human TonEBP
(T), NFAT1(N), and NF-  B
p52 (P) in the DNA-binding region. The numbering for TonEBP is
used. The secondary structure assignments for TonEBP are shown
as colored bars (  -helices)
and arrows (  -strands)
above the aligned sequences; those for NF- B
p52 are shown below the sequence. The colored blocks show
residues that participate in contacts to DNA (magenta), RHR-C
dimerization (green) and E'F loop dimerization (yellow).
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Figure 3.
Figure 3. Dimerization in the TonEBP -DNA complex. a, The
C-terminal dimer interface viewed in the same orientation as
Fig. 1a. Hydrophobic residues Leu 372, Ile 390, Leu 422, Ile
429, and Phe 388 from each TonEBP monomer form the center of the
interface. Polar residues Asn 426, His 424, His 427, Lys 373,
Glu 386, and Ser 375 from each monomer form the peripheral of
the interface through networks of hydrogen bonding and
electrostatic interactions. b, The N-terminal dimer interface
viewed from underneath the DNA with respect to Fig. 1a. The -helix
of the E'F loop from each monomer supplies residues for
dimerization, which include Arg 315, Ala 317, Asp 318, and Glu
320. The conformation of the -helix
is stabilized by the DNA backbone (N-terminal capping) and by
the hydrophobic interactions with the main body of the protein
through residues Val 321, Leu 312, and Phe 267. c,
Simulated-annealing omit map showing the electron density of the
E'F dimer interface residues (Arg 315, Asn 316, Ala 317, Asp
318, Val 319, and Glu 320) in stereo. The 2.86 Å  [A]-weighted
F[o] - F[c] map is contoured at 2.0 level.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2002,
9,
90-94)
copyright 2002.
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