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PDBsum entry 2v6c
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Transcription regulator
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PDB id
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2v6c
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References listed in PDB file
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Key reference
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Title
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Structural insights into the transcriptional and translational roles of ebp1.
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Authors
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T.P.Monie,
A.J.Perrin,
J.R.Birtley,
T.R.Sweeney,
I.Karakasiliotis,
Y.Chaudhry,
L.O.Roberts,
S.Matthews,
I.G.Goodfellow,
S.Curry.
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Ref.
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EMBO J, 2007,
26,
3936-3944.
[DOI no: ]
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PubMed id
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Abstract
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The ErbB3-binding protein 1 (Ebp1) is an important regulator of transcription,
affecting eukaryotic cell growth, proliferation, differentiation and survival.
Ebp1 can also affect translation and cooperates with the polypyrimidine
tract-binding protein (PTB) to stimulate the activity of the internal ribosome
entry site (IRES) of foot-and-mouth disease virus (FMDV). We report here the
crystal structure of murine Ebp1 (p48 isoform), providing the first glimpse of
the architecture of this versatile regulator. The structure reveals a core
domain that is homologous to methionine aminopeptidases, coupled to a C-terminal
extension that contains important motifs for binding proteins and RNA. It sheds
new light on the conformational differences between the p42 and p48 isoforms of
Ebp1, the disposition of the key protein-interacting motif ((354)LKALL(358)) and
the RNA-binding activity of Ebp1. We show that the primary RNA-binding site is
formed by a Lys-rich motif in the C terminus and mediates the interaction with
the FMDV IRES. We also demonstrate a specific functional requirement for Ebp1 in
FMDV IRES-directed translation that is independent of a direct interaction with
PTB.
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Figure 1.
Figure 1 Molecular structure of Ebp1 and comparison with a type
II human MAP (hMAP2). (A) Ribbon diagram of the crystal
structure of Ebp1(8–360);  -helices
are coloured pink and  -strands
blue. (B) Superposition of Ebp1 in orange and hMAP2 in cyan (PDB
1kq9 (Nonato et al, 2006)); insertions in Ebp1 are coloured dark
red and those in hMAP2 dark blue. (C–E) Comparison of the
active site of hMAP2 with the corresponding region in Ebp1. Side
chains of selected residues are shown as sticks for (C) hMAP2,
(D) a superposition of hMAP2 and Ebp1 and (E) Ebp1. The colour
coding is the same as for panel B.
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Figure 5.
Figure 5 Structural features at the N and C termini of Ebp1. (A)
The structure shows that the predicted p42 isoform (left) which
starts at Met 55 lacks one and a half helices at the N terminus
of the p48 isoform (indicated in grey in the structure on the
right). This helix makes extensive hydrophobic contacts with the
body of Ebp1 (coloured by atom type: carbon—orange;
nitrogen—blue oxygen—red; sulphur—yellow); its removal
exposes a large hydrophobic cleft on one face of the protein.
The structure of p48 Ebp1 also illustrates the proximity of K20
and K22 to the lys-rich loop 1; together these features may
constitute a bipartite nucleolar localisation signal (Squatrito
et al, 2004; Fujiwara et al, 2006). (B) Position of the
^354LKALL^358 protein-binding motif at the C terminus of Ebp1.
Colouring is the same as in Figure 1B except that residues from
the motifs are highlighted in green. The surface of Ebp1 up to
residue 337 is shown. Close-up views (in similar orientations)
of the LxxLL motif from (C) Ebp1 and (D) the AR ((Hur et al,
2004); PDB—1t7f). Residues from Ebp1 are colour coded as
described above. Carbon atoms of the LxxLL motif of the peptide
ligand of AR are cyan.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2007,
26,
3936-3944)
copyright 2007.
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