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PDBsum entry 1yae
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Membrane protein
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PDB id
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1yae
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References listed in PDB file
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Key reference
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Title
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Structure of the kainate receptor subunit glur6 agonist-Binding domain complexed with domoic acid.
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Authors
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M.H.Nanao,
T.Green,
Y.Stern-Bach,
S.F.Heinemann,
S.Choe.
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Ref.
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Proc Natl Acad Sci U S A, 2005,
102,
1708-1713.
[DOI no: ]
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PubMed id
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Abstract
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We report the crystal structure of the glycosylated ligand-binding (S1S2) domain
of the kainate receptor subunit GluR6, in complex with the agonist domoate. The
structure shows the expected overall homology with AMPA and NMDA receptor
subunit structures but reveals an unexpected binding mode for the side chain of
domoate, in which contact is made to the larger lobe only (lobe I). In common
with the AMPA receptor subunit GluR2, the GluR6 S1S2 domain associates as a
dimer, with many of the interdimer contacts being conserved. Subtle differences
in these contacts provide a structural explanation for why GluR2 L483Y and GluR3
L507Y are nondesensitizing, but GluR6, which has a tyrosine at that site, is
not. The structure incorporates native glycosylation, which has not previously
been described for ionotropic glutamate receptors. The position of the sugars
near the subunit interface rules out their direct involvement in subunit
association but leaves open the possibility of indirect modulation. Finally, we
observed several tetrameric assemblies that satisfy topological constraints with
respect to connection to the receptor pore, and which are therefore candidates
for the native quaternary structure.
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Figure 2.
Fig. 2. The structure determined for GluR6 S1S2 (protomer
a) is shown in two views  90° apart. S1 is
colored yellow, and S2 is blue. The N-acetylglucosamine-fucose
sugar moieties modeled at N423 (gray) and domoate (orange) are
shown in stick representation. Labels indicate the relative
location of the chains within the full-length subunit, lobes I
and II, and the construct N and C termini. *, helix 774-788.
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Figure 4.
Fig. 4. Views of the AMPA-like dimer interface in GluR6 and
GluR2. The interface between dimers is highlighted by shading.
Structures were aligned over lobe I only. (A) Density is shown
around residues K531 and T779 (protomer c on the left) and
residues E524 F529 (protomer e on the right). A polar
interaction is observed between the T779 side chain and the K531
main chain nitrogen. (B) The same view of GluR6 (green residue
labels) is shown aligned with GluR2 protomers a and c (AMPA
complex, carbons, and residue labels in gray). GluR2 N747 forms
hydrogen bonds with both the K493 main chain and the E486 side
chain. (C) An interaction observed only in GluR6 is shown for
the same protomer pairs (GluR6, green cartoon; GluR2, purple
cartoon), looking down the twofold axis from lobe I. GluR6
residues R775 and D776 (yellow; green labels) and GluR2 residues
G743 and G743 and N744 (orange; purple label) are highlighted.
There is a clear movement of helix 774-788 (arrowheads) compared
with the equivalent helix in GluR2 (742-755). (D) The
environment around GluR6 residue Y521 in the dimer formed by
protomer a with itself (green carbons) is shown compared with
the equivalent residues in wild-type GluR2 (gray carbons) and
GluR2 L483Y (1LB8; red carbons). Residues Y521 to K525 are shown
on the left (residues L/Y483 to E487 in GluR2) and I780 to Q784
(L748 to K752 in GluR2) on the right. For clarity, side chains
are shown only for the first and last residues in each chain.
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