|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Membrane protein
|
|
|
Title:
|
|
Structure of the kainate receptor subunit glur6 agonist binding domain complexed with domoic acid
|
|
Structure:
|
|
Glutamate receptor, ionotropic kainate 2. Chain: a, b, c, d, e, f. Fragment: subunit glur6 agonist binding domain with the transmembrane domain removed and replaced with a hydrophilic linker. Synonym: kainate receptor, glutamate receptor 6, glur-6, glur6, excitatory amino acid receptor 4, eaa4. Engineered: yes. Other_details: transmembrane domain was removed and replaced with a hydrophilic linker
|
|
Source:
|
|
Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: trichoplusia ni. Expression_system_taxid: 7111
|
|
Biol. unit:
|
|
Hexamer (from
)
|
|
Resolution:
|
|
|
3.11Å
|
R-factor:
|
0.278
|
R-free:
|
0.334
|
|
|
Authors:
|
|
M.H.Nanao,T.Green,Y.Stern-Bach,S.F.Heinemann,S.Choe
|
Key ref:
|
|
M.H.Nanao
et al.
(2005).
Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid.
Proc Natl Acad Sci U S A,
102,
1708-1713.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
17-Dec-04
|
Release date:
|
01-Feb-05
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Proc Natl Acad Sci U S A
102:1708-1713
(2005)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid.
|
|
M.H.Nanao,
T.Green,
Y.Stern-Bach,
S.F.Heinemann,
S.Choe.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
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.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
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.
|
|
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.
|
|
|
|
| |
Figures were
selected
by the author.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
G.Lemière,
S.Sedehizadeh,
J.Toueg,
N.Fleary-Roberts,
and
J.Clayden
(2011).
A general synthetic approach to the amnesic shellfish toxins: total synthesis of (-)-isodomoic acid B, (-)-isodomoic acid E and (-)-isodomoic acid F.
|
| |
Chem Commun (Camb),
47,
3745-3747.
|
|
|
|
|
|
|
G.M.Alushin,
D.Jane,
and
M.L.Mayer
(2011).
Binding site and ligand flexibility revealed by high resolution crystal structures of GluK1 competitive antagonists.
|
| |
Neuropharmacology,
60,
126-134.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
L.Abuin,
B.Bargeton,
M.H.Ulbrich,
E.Y.Isacoff,
S.Kellenberger,
and
R.Benton
(2011).
Functional architecture of olfactory ionotropic glutamate receptors.
|
| |
Neuron,
69,
44-60.
|
|
|
|
|
|
|
W.H.Zhou,
X.C.Guo,
H.Q.Zhao,
S.X.Wu,
H.H.Yang,
and
X.R.Wang
(2011).
Molecularly imprinted polymer for selective extraction of domoic acid from seafood coupled with high-performance liquid chromatographic determination.
|
| |
Talanta,
84,
777-782.
|
|
|
|
|
|
|
A.H.Ahmed,
and
R.E.Oswald
(2010).
Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.
|
| |
J Med Chem,
53,
2197-2203.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.Vijayan,
M.A.Sahai,
T.Czajkowski,
and
P.C.Biggin
(2010).
A comparative analysis of the role of water in the binding pockets of ionotropic glutamate receptors.
|
| |
Phys Chem Chem Phys,
12,
14057-14066.
|
|
|
|
|
|
|
T.Nakagawa
(2010).
The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors.
|
| |
Mol Neurobiol,
42,
161-184.
|
|
|
|
|
|
|
U.Das,
J.Kumar,
M.L.Mayer,
and
A.J.Plested
(2010).
Domain organization and function in GluK2 subtype kainate receptors.
|
| |
Proc Natl Acad Sci U S A,
107,
8463-8468.
|
|
|
|
|
|
|
A.H.Ahmed,
Q.Wang,
H.Sondermann,
and
R.E.Oswald
(2009).
Structure of the S1S2 glutamate binding domain of GLuR3.
|
| |
Proteins,
75,
628-637.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
C.Chaudhry,
A.J.Plested,
P.Schuck,
and
M.L.Mayer
(2009).
Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions.
|
| |
Proc Natl Acad Sci U S A,
106,
12329-12334.
|
|
|
|
|
|
|
C.Chaudhry,
M.C.Weston,
P.Schuck,
C.Rosenmund,
and
M.L.Mayer
(2009).
Stability of ligand-binding domain dimer assembly controls kainate receptor desensitization.
|
| |
EMBO J,
28,
1518-1530.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
L.Bunch,
and
P.Krogsgaard-Larsen
(2009).
Subtype selective kainic acid receptor agonists: discovery and approaches to rational design.
|
| |
Med Res Rev,
29,
3.
|
|
|
|
|
|
|
M.Du,
A.Rambhadran,
and
V.Jayaraman
(2009).
Vibrational spectroscopic investigation of the ligand binding domain of kainate receptors.
|
| |
Protein Sci,
18,
1585-1591.
|
|
|
|
|
|
|
N.Nayeem,
Y.Zhang,
D.K.Schweppe,
D.R.Madden,
and
T.Green
(2009).
A nondesensitizing kainate receptor point mutant.
|
| |
Mol Pharmacol,
76,
534-542.
|
|
|
|
|
|
|
W.Zhang,
F.St-Gelais,
C.P.Grabner,
J.C.Trinidad,
A.Sumioka,
M.Morimoto-Tomita,
K.S.Kim,
C.Straub,
A.L.Burlingame,
J.R.Howe,
and
S.Tomita
(2009).
A transmembrane accessory subunit that modulates kainate-type glutamate receptors.
|
| |
Neuron,
61,
385-396.
|
|
|
|
|
|
|
A.Gill,
A.Birdsey-Benson,
B.L.Jones,
L.P.Henderson,
and
D.R.Madden
(2008).
Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists.
|
| |
Biochemistry,
47,
13831-13841.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
E.J.Bjerrum,
and
P.C.Biggin
(2008).
Rigid body essential X-ray crystallography: distinguishing the bend and twist of glutamate receptor ligand binding domains.
|
| |
Proteins,
72,
434-446.
|
|
|
|
|
|
|
L.L.Lash,
J.M.Sanders,
N.Akiyama,
M.Shoji,
P.Postila,
O.T.Pentikäinen,
M.Sasaki,
R.Sakai,
and
G.T.Swanson
(2008).
Novel analogs and stereoisomers of the marine toxin neodysiherbaine with specificity for kainate receptors.
|
| |
J Pharmacol Exp Ther,
324,
484-496.
|
|
|
|
|
|
|
M.Du,
A.Rambhadran,
and
V.Jayaraman
(2008).
Luminescence resonance energy transfer investigation of conformational changes in the ligand binding domain of a kainate receptor.
|
| |
J Biol Chem,
283,
27074-27078.
|
|
|
|
|
|
|
S.M.Schmid,
and
M.Hollmann
(2008).
To gate or not to gate: are the delta subunits in the glutamate receptor family functional ion channels?
|
| |
Mol Neurobiol,
37,
126-141.
|
|
|
|
|
|
|
Y.Yao,
C.B.Harrison,
P.L.Freddolino,
K.Schulten,
and
M.L.Mayer
(2008).
Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors.
|
| |
EMBO J,
27,
2158-2170.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
I.H.Greger,
E.B.Ziff,
and
A.C.Penn
(2007).
Molecular determinants of AMPA receptor subunit assembly.
|
| |
Trends Neurosci,
30,
407-416.
|
|
|
|
|
|
|
P.B.Bernard,
D.S.Macdonald,
D.A.Gill,
C.L.Ryan,
and
R.A.Tasker
(2007).
Hippocampal mossy fiber sprouting and elevated trkB receptor expression following systemic administration of low dose domoic acid during neonatal development.
|
| |
Hippocampus,
17,
1121-1133.
|
|
|
|
|
|
|
A.Priel,
S.Selak,
J.Lerma,
and
Y.Stern-Bach
(2006).
Block of kainate receptor desensitization uncovers a key trafficking checkpoint.
|
| |
Neuron,
52,
1037-1046.
|
|
|
|
|
|
|
A.S.Kristensen,
M.T.Geballe,
J.P.Snyder,
and
S.F.Traynelis
(2006).
Glutamate receptors: variation in structure-function coupling.
|
| |
Trends Pharmacol Sci,
27,
65-69.
|
|
|
|
|
|
|
C.Vale-González,
A.Alfonso,
C.Suñol,
M.R.Vieytes,
and
L.M.Botana
(2006).
Role of the plasma membrane calcium adenosine triphosphatase on domoate-induced intracellular acidification in primary cultures of cerebelar granule cells.
|
| |
J Neurosci Res,
84,
326-337.
|
|
|
|
|
|
|
I.H.Greger,
P.Akamine,
L.Khatri,
and
E.B.Ziff
(2006).
Developmentally regulated, combinatorial RNA processing modulates AMPA receptor biogenesis.
|
| |
Neuron,
51,
85-97.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.C.Weston,
P.Schuck,
A.Ghosal,
C.Rosenmund,
and
M.L.Mayer
(2006).
Conformational restriction blocks glutamate receptor desensitization.
|
| |
Nat Struct Mol Biol,
13,
1120-1127.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Volgraf,
P.Gorostiza,
R.Numano,
R.H.Kramer,
E.Y.Isacoff,
and
D.Trauner
(2006).
Allosteric control of an ionotropic glutamate receptor with an optical switch.
|
| |
Nat Chem Biol,
2,
47-52.
|
|
|
|
|
|
|
P.E.Chen,
and
D.J.Wyllie
(2006).
Pharmacological insights obtained from structure-function studies of ionotropic glutamate receptors.
|
| |
Br J Pharmacol,
147,
839-853.
|
|
|
|
|
|
|
P.Pinheiro,
and
C.Mulle
(2006).
Kainate receptors.
|
| |
Cell Tissue Res,
326,
457-482.
|
|
|
|
|
|
|
U.Pentikäinen,
L.Settimo,
M.S.Johnson,
and
O.T.Pentikäinen
(2006).
Subtype selectivity and flexibility of ionotropic glutamate receptors upon antagonist ligand binding.
|
| |
Org Biomol Chem,
4,
1058-1070.
|
|
|
|
|
|
|
H.Furukawa,
S.K.Singh,
R.Mancusso,
and
E.Gouaux
(2005).
Subunit arrangement and function in NMDA receptors.
|
| |
Nature,
438,
185-192.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.L.Mayer
(2005).
Glutamate receptor ion channels.
|
| |
Curr Opin Neurobiol,
15,
282-288.
|
|
|
|
|
|
|
R.H.Kramer,
J.J.Chambers,
and
D.Trauner
(2005).
Photochemical tools for remote control of ion channels in excitable cells.
|
| |
Nat Chem Biol,
1,
360-365.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
 |
Links
