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PDBsum entry 1rk8
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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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Molecular insights into the interaction of pym with the mago-Y14 core of the exon junction complex.
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Authors
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F.Bono,
J.Ebert,
L.Unterholzner,
T.Güttler,
E.Izaurralde,
E.Conti.
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Ref.
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EMBO Rep, 2004,
5,
304-310.
[DOI no: ]
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PubMed id
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Abstract
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The exon junction complex (EJC) is deposited on mRNAs as a consequence of
splicing and influences postsplicing mRNA metabolism. The Mago-Y14 heterodimer
is a core component of the EJC. Recently, the protein PYM has been identified as
an interacting partner of Mago-Y14. Here we show that PYM is a cytoplasmic
RNA-binding protein that is excluded from the nucleus by Crm1. PYM interacts
directly with Mago-Y14 by means of its N-terminal domain. The crystal structure
of the Drosophila ternary complex at 1.9 A resolution reveals that PYM binds
Mago and Y14 simultaneously, capping their heterodimerization interface at
conserved surface residues. Formation of this ternary complex is also observed
with the human proteins. Mago residues involved in the interaction with PYM have
been implicated in nonsense-mediated mRNA decay (NMD). Consistently, human PYM
is active in NMD tethering assays. Together, these data suggest a role for PYM
in NMD.
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Figure 3.
Figure 3 PYM binds Mago -Y14 with extensive interactions. (A)
Schematic view of the PYM -Mago -Y14 complex (left panel) and
schematic diagram highlighting the key residues involved in the
interaction (right panel). Positively charged residues of PYM
interact with negatively charged residues of Mago helices  1
and 2.
In addition, PYM interacts with the  2
- 3
loop of Y14 by means of hydrophobic contacts. Colours are as in
Fig 2. Hydrogen bonds are shown with dotted lines. (B) Stereo
representation of the structure and of the interacting residues
in a similar orientation as in Figs 2A,3A.
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Figure 4.
Figure 4 The PYM -Mago -Y14 complex is conserved across species.
(A) The interaction surfaces of D. melanogaster PYM and the Mago
-Y14 heterodimer have been opened up relative to the view in Fig
2A. The two surfaces are coloured according to sequence
conservation, ranging from orange for conserved residues to
white for variable residues. On the right, the atomic model of
PYM is shown bound to the surface of Mago -Y14. (B) Lysates
prepared from E. coli expressing untagged H. sapiens (Hs) PYM
were incubated with glutathione agarose beads coated with GST,
GST -Hs Y14, GST -Hs Mago or GST -Hs Y14 -Mago dimers.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO Rep
(2004,
5,
304-310)
copyright 2004.
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