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PDBsum entry 2j0s
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Contents |
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391 a.a.
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143 a.a.
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89 a.a.
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44 a.a.
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References listed in PDB file
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Key reference
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Title
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The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA.
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Authors
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F.Bono,
J.Ebert,
E.Lorentzen,
E.Conti.
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Ref.
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Cell, 2006,
126,
713-725.
[DOI no: ]
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PubMed id
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Abstract
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The exon junction complex (EJC) plays a major role in posttranscriptional
regulation of mRNA in metazoa. The EJC is deposited onto mRNA during splicing
and is transported to the cytoplasm where it influences translation,
surveillance, and localization of the spliced mRNA. The complex is formed by the
association of four proteins (eIF4AIII, Barentsz [Btz], Mago, and Y14), mRNA,
and ATP. The 2.2 A resolution structure of the EJC reveals how it stably locks
onto mRNA. The DEAD-box protein eIF4AIII encloses an ATP molecule and provides
the binding sites for six ribonucleotides. Btz wraps around eIF4AIII and stacks
against the 5' nucleotide. An intertwined network of interactions anchors
Mago-Y14 and Btz at the interface between the two domains of eIF4AIII,
effectively stabilizing the ATP bound state. Comparison with the structure of
the eIF4AIII-Btz subcomplex that we have also determined reveals that large
conformational changes are required upon EJC assembly and disassembly.
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Figure 2.
Figure 2. Structure of EJC
View of the human EJC in two
orientations related by a 180° rotation about a vertical
axis. In the complex, Btz (shown in red) stretches around the
DEAD-box helicase eIF4AIII (in yellow). Both proteins interact
with RNA (in black), which is bound at a cleft formed between
the two RecA-like domains of eIF4AIII. ATP (in gray) binds at an
interface between the two domains of eIF4AIII, distinct from the
RNA binding cleft. The other two protein components of the EJC,
Mago (blue), and Y14 (magenta), bind mainly to domain 2 of
eIF4AIII, but the interaction surface also extends over to the
interface with domain 1. The dotted line in red shows the
approximate path of a portion of Btz not present in the electron
density (residues 198–213; Figure 1). The helix at the
C-terminal stretch of Btz is present in the 3.2 Å
resolution structure (shown), while it is partially disordered
in the 2.2 Å structure. The two EJC structures are
otherwise virtually identical. All ribbon drawings were rendered
using PyMOL (DeLano, W.L., 2002, http://www.pymol.org).
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Figure 4.
Figure 4. Interaction Networks between the Protein Components
of the EJC
(A) The C-terminal stretch of Btz (red) is
anchored to domain 1 of eIF4AIII (yellow). The close up is in a
similar orientation as Figure 2A. It shows a subset of Btz
residues contacting a region of the DEAD-box protein that is
conserved in eIF4AIII orthologs but not in paralogs such as
eIF4AI.
(B) Group of interactions between Mago (blue), Btz,
and eIF4AIII. Mago and Btz protrude into the cleft that is
formed between the two domains of eIF4AIII.
(C) The
C-terminal helix of eIF4AIII engages in a cluster of
interactions between Y14 (magenta) and Mago.
(D)
Interactions of Mago-Y14 with the eIF4AIII linker (residues
241–250, in yellow) connecting the two RecA-like domains (in
gray). The linker is wedged into Mago-Y14. It interacts on one
side with the loops of Mago shown in panel (B) and on the other
side with Y14 and with the C-terminal region of Mago (see Ile146
in Figure 3E).
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
126,
713-725)
copyright 2006.
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