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PDBsum entry 1rgo
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RNA binding protein
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PDB id
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1rgo
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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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Recognition of the mRNA au-Rich element by the zinc finger domain of tis11d.
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Authors
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B.P.Hudson,
M.A.Martinez-Yamout,
H.J.Dyson,
P.E.Wright.
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Ref.
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Nat Struct Mol Biol, 2004,
11,
257-264.
[DOI no: ]
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PubMed id
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Abstract
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The tandem zinc finger (TZF) domain of the protein TIS11d binds to the class II
AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and
promotes their deadenylation and degradation. The NMR structure of the TIS11d
TZF domain bound to the RNA sequence 5'-UUAUUUAUU-3' comprises a pair of novel
CCCH fingers of type CX(8)CX(5)CX(3)H separated by an 18-residue linker. The two
TIS11d zinc fingers bind in a symmetrical fashion to adjacent 5'-UAUU-3'
subsites on the single-stranded RNA via a combination of electrostatic and
hydrogen-bonding interactions, with intercalative stacking between conserved
aromatic side chains and the RNA bases. Sequence specificity in RNA recognition
is achieved by a network of intermolecular hydrogen bonds, mostly between TIS11d
main-chain functional groups and the Watson-Crick edges of the bases. The TIS11d
structure provides insights into the RNA-binding functions of this large family
of CCCH zinc finger proteins.
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Figure 3.
Figure 3. Solution structure of the RNA complex of TIS11d.
(a) Stereo view of the best 20 structures superposed on backbone
heavy atoms in ordered regions of the protein and RNA. The
protein backbone is blue, the RNA backbone red, and RNA bases
yellow. For clarity, only ordered regions of TIS11d (residues
153 -217) and RNA bases U2 -U9 are shown. (b) Ribbon
representation of a single structure, in the same orientation as
in a, showing the location and coordination of zinc in each of
the fingers. Colors are the same as in a, with the addition of
green side chains for the zinc-coordinating ligands. (c)
Backbone superposition of the structure ensembles of fingers 1
and 2. Finger 1 (Arg153 -Phe180) is dark blue (backbone), green
(zinc-coordinating side chains) and red (intercalating aromatic
rings); the bound RNA (U6, A7, U8, U9) is orange. The
corresponding colors for finger 2 are light blue, yellow, pink
and yellow. Figures were generated using MolMol50.
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Figure 4.
Figure 4. Molecular recognition of RNA by TIS11d and hydrogen
bonding between TIS11d and RNA. (a) Molecular contact surface
of a representative TIS11d TZF structure generated in GRASP51
showing surface topology. Green denotes convex surfaces. The
locations of the (R/K)YKTEL motifs that form the U6 and U2
binding pockets are indicated. (b) Stereo view showing
hydrogen-bonding interactions between finger 1 and the 3' UAUU
subsite. The protein backbone is light blue, the RNA backbone
and bases pale yellow, and the intercalating aromatic side
chains green. Each of the intermolecular hydrogen bonds is
designated with a number and identified by a red line and
colored atoms (red, oxygen; white, hydrogen; blue, nitrogen).
(c) Schematic figure summarizing hydrogen-bonding interactions
(dotted lines) with each of the bases in both subsites of the
ARE. The hydrogen bond numbers for finger 1 in part b are shown.
Panels a and b were generated using MolMol50.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2004,
11,
257-264)
copyright 2004.
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