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PDBsum entry 2uxa
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Membrane protein
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PDB id
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2uxa
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References listed in PDB file
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Key reference
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Title
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Developmentally regulated, Combinatorial RNA processing modulates ampa receptor biogenesis.
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Authors
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I.H.Greger,
P.Akamine,
L.Khatri,
E.B.Ziff.
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Ref.
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Neuron, 2006,
51,
85-97.
[DOI no: ]
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PubMed id
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Abstract
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The subunit composition determines AMPA receptor (AMPA-R) function and
trafficking. Mechanisms underlying channel assembly are thus central to the
efficacy and plasticity of glutamatergic synapses. We previously showed that RNA
editing at the Q/R site of the GluR2 subunit contributes to the assembly of
AMPA-R heteromers by attenuating formation of GluR2 homotetramers. Here we
report that this function of the Q/R site depends on subunit contacts between
adjacent ligand binding domains (LBDs). Changes of LBD interface contacts alter
GluR2 assembly properties, forward traffic, and expression at synapses.
Interestingly, developmentally regulated RNA editing within the LBD (at the R/G
site) produces analogous effects. Our data reveal that editing to glycine
reduces the self-assembly competence of this critical subunit and slows GluR2
maturation in the endoplasmic reticulum (ER). Therefore, RNA editing sites,
located at strategic subunit interfaces, shape AMPA-R assembly and trafficking
in a developmentally regulated manner.
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Figure 4.
Figure 4. The Crystal Structure of the R2i-R LBD Reveals
Closely Opposed Arg743 Side Chains; C ζ Distance = 3.9 Å
(A) Sequence alignment depicting amino acid changes between
flip and flop, starting at position 744; the R/G site (743) is
shown in bold. Alternative residues are indicated in color.
Helices J and K (light blue bars) are drawn above the sequences.
Note that the cluster of changes comprising position 775–779
is not included in the structure.
(B) Side view of the
glutamate-bound flip/R LBD dimer. The two subunits are color
coded (chain A in cyan, chain C in yellow). Arg743 is indicated
in stick.
(C) Superposition of the flip/R (yellow) and
flop/G LBDs (gray; top view). Alternative residues, 743–745,
are shown in stick: flip residues, black; flop residues, white;
positions are indicated on one protomer only. Helices D and J
are denoted.
(D) Fo-Fc electron densities for Arg743 side
chains. Contour level was 0.16 e/Å^3. The figure was drawn
with CCP4mg.
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Figure 5.
Figure 5. Electrostatic Environment of Arg743
(A) Side
view of the flip/R LBD colored by solvent-accessible surface
area. Accessible residues range from white (fully accessible) to
gray; inaccessible positions are depicted in blue. Green spheres
denote water molecules. The red asterisk marks Arg743 residues.
The figure was generated with CCP4mg.
(B) Image depicting
the solvent network (red spheres) bridging the Arg743 side
chains.
(C) Surface views outlining the electrostatic
environment of the R/G site. Counter-charges (E486, D490, T744)
within a 6.5 Å radius of Nη743 are indicated. Top views
of the flip/R (left) and flop/G LBD (right). Arg743 side chains
(gray) were superimposed onto the flop/G LBD to illustrate the
gap generated by editing to Gly; the black dot marks N744.
Protomers were color coded—chain A, yellow; chain C, gray.
Panels (B) and (C) were drawn with PyMOL (DeLano, 2002).
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The above figures are
reprinted
by permission from Cell Press:
Neuron
(2006,
51,
85-97)
copyright 2006.
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