 |
PDBsum entry 1tt1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane protein
|
PDB id
|
|
|
|
1tt1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Neuron
45:539-552
(2005)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity.
|
|
M.L.Mayer.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Little is known about the molecular mechanisms underlying differences in the
ligand binding properties of AMPA, kainate, and NMDA subtype glutamate
receptors. Crystal structures of the GluR5 and GluR6 kainate receptor ligand
binding cores in complexes with glutamate, 2S,4R-4-methylglutamate, kainate, and
quisqualate have now been solved. The structures reveal that the ligand binding
cavities are 40% (GluR5) and 16% (GluR6) larger than for GluR2. The binding of
AMPA- and GluR5-selective agonists to GluR6 is prevented by steric occlusion,
which also interferes with the high-affinity binding of 2S,4R-4-methylglutamate
to AMPA receptors. Strikingly, the extent of domain closure produced by the
GluR6 partial agonist kainate is only 3 degrees less than for glutamate and 11
degrees greater than for the GluR2 kainate complex. This, together with
extensive interdomain contacts between domains 1 and 2 of GluR5 and GluR6,
absent from AMPA receptors, likely contributes to the high stability of GluR5
and GluR6 kainate complexes.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 4.
Figure 4. Docking GluR5-Selective Ligands in the GluR6 and
GluR5 Ligand Binding Sites
|
|
Figure 7.
Figure 7. Interdomain Contacts in GluR5 and GluR2
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from Cell Press:
Neuron
(2005,
45,
539-552)
copyright 2005.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
D.Stroebel,
S.Carvalho,
and
P.Paoletti
(2011).
Functional evidence for a twisted conformation of the NMDA receptor GluN2A subunit N-terminal domain.
|
| |
Neuropharmacology,
60,
151-158.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
J.L.Rasmussen,
M.Storgaard,
D.S.Pickering,
and
L.Bunch
(2011).
Rational Design, Synthesis and Pharmacological Evaluation of the (2R)- and (2S)-Stereoisomers of 3-(2-Carboxypyrrolidinyl)-2-methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors.
|
| |
ChemMedChem,
6,
498-504.
|
|
|
|
|
|
|
M.L.Mayer
(2011).
Glutamate receptor ion channels: where do all the calories go?
|
| |
Nat Struct Mol Biol,
18,
253-254.
|
|
|
|
|
|
|
A.H.Ahmed,
C.P.Ptak,
and
R.E.Oswald
(2010).
Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA.
|
| |
Biochemistry,
49,
2843-2850.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
D.Perrais,
J.Veran,
and
C.Mulle
(2010).
Gating and permeation of kainate receptors: differences unveiled.
|
| |
Trends Pharmacol Sci,
31,
516-522.
|
|
|
|
|
|
|
L.L.Lash-Van Wyhe,
P.A.Postila,
K.Tsubone,
M.Sasaki,
O.T.Pentikäinen,
R.Sakai,
and
G.T.Swanson
(2010).
Pharmacological activity of C10-substituted analogs of the high-affinity kainate receptor agonist dysiherbaine.
|
| |
Neuropharmacology,
58,
640-649.
|
|
|
|
|
|
|
P.A.Postila,
G.T.Swanson,
and
O.T.Pentikäinen
(2010).
Exploring kainate receptor pharmacology using molecular dynamics simulations.
|
| |
Neuropharmacology,
58,
515-527.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
A.I.Sobolevsky,
M.P.Rosconi,
and
E.Gouaux
(2009).
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor.
|
| |
Nature,
462,
745-756.
|
|
|
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:
|
|
|
|
|
|
|
|
E.Karakas,
N.Simorowski,
and
H.Furukawa
(2009).
Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit.
|
| |
EMBO J,
28,
3910-3920.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
G.T.Swanson,
and
R.Sakai
(2009).
Ligands for ionotropic glutamate receptors.
|
| |
Prog Mol Subcell Biol,
46,
123-157.
|
|
|
|
|
|
|
J.Kumar,
P.Schuck,
R.Jin,
and
M.L.Mayer
(2009).
The N-terminal domain of GluR6-subtype glutamate receptor ion channels.
|
| |
Nat Struct Mol Biol,
16,
631-638.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
K.Frydenvang,
L.L.Lash,
P.Naur,
P.A.Postila,
D.S.Pickering,
C.M.Smith,
M.Gajhede,
M.Sasaki,
R.Sakai,
O.T.Pentikaïnen,
G.T.Swanson,
and
J.S.Kastrup
(2009).
Full Domain Closure of the Ligand-binding Core of the Ionotropic Glutamate Receptor iGluR5 Induced by the High Affinity Agonist Dysiherbaine and the Functional Antagonist 8,9-Dideoxyneodysiherbaine.
|
| |
J Biol Chem,
284,
14219-14229.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
K.Speranskiy,
and
M.G.Kurnikova
(2009).
Modeling of peptides connecting the ligand-binding and transmembrane domains in the GluR2 glutamate receptor.
|
| |
Proteins,
76,
271-280.
|
|
|
|
|
|
|
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.B.Gill,
P.Vivithanaporn,
and
G.T.Swanson
(2009).
Glutamate Binding and Conformational Flexibility of Ligand-binding Domains Are Critical Early Determinants of Efficient Kainate Receptor Biogenesis.
|
| |
J Biol Chem,
284,
14503-14512.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
R.Benton,
K.S.Vannice,
C.Gomez-Diaz,
and
L.B.Vosshall
(2009).
Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila.
|
| |
Cell,
136,
149-162.
|
|
|
|
|
|
|
R.Numano,
S.Szobota,
A.Y.Lau,
P.Gorostiza,
M.Volgraf,
B.Roux,
D.Trauner,
and
E.Y.Isacoff
(2009).
Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR.
|
| |
Proc Natl Acad Sci U S A,
106,
6814-6819.
|
|
|
|
|
|
|
S.B.Lee,
C.H.Lee,
S.N.Kim,
K.M.Chung,
Y.K.Cho,
and
K.N.Kim
(2009).
Type II and III Taste Bud Cells Preferentially Expressed Kainate Glutamate Receptors in Rats.
|
| |
Korean J Physiol Pharmacol,
13,
455-460.
|
|
|
|
|
|
|
S.L.Dargan,
V.R.Clarke,
G.M.Alushin,
J.L.Sherwood,
R.Nisticò,
Z.A.Bortolotto,
A.M.Ogden,
D.Bleakman,
A.J.Doherty,
D.Lodge,
M.L.Mayer,
S.M.Fitzjohn,
D.E.Jane,
and
G.L.Collingridge
(2009).
ACET is a highly potent and specific kainate receptor antagonist: characterisation and effects on hippocampal mossy fibre function.
|
| |
Neuropharmacology,
56,
121-130.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
A.J.Plested,
R.Vijayan,
P.C.Biggin,
and
M.L.Mayer
(2008).
Molecular basis of kainate receptor modulation by sodium.
|
| |
Neuron,
58,
720-735.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
C.Villmann,
J.Hoffmann,
M.Werner,
S.Kott,
N.Strutz-Seebohm,
T.Nilsson,
and
M.Hollmann
(2008).
Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors.
|
| |
J Neurochem,
107,
453-465.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
M.L.Blanke,
and
A.M.VanDongen
(2008).
Constitutive activation of the N-methyl-D-aspartate receptor via cleft-spanning disulfide bonds.
|
| |
J Biol Chem,
283,
21519-21529.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
T.J.Wilding,
E.Fulling,
Y.Zhou,
and
J.E.Huettner
(2008).
Amino acid substitutions in the pore helix of GluR6 control inhibition by membrane fatty acids.
|
| |
J Gen Physiol,
132,
85-99.
|
|
|
|
|
|
|
T.Mamonova,
M.J.Yonkunas,
and
M.G.Kurnikova
(2008).
Energetics of the cleft closing transition and the role of electrostatic interactions in conformational rearrangements of the glutamate receptor ligand binding domain.
|
| |
Biochemistry,
47,
11077-11085.
|
|
|
|
|
|
|
X.Han,
H.Tomitori,
S.Mizuno,
K.Higashi,
C.Füll,
T.Fukiwake,
Y.Terui,
P.Leewanich,
K.Nishimura,
T.Toida,
K.Williams,
K.Kashiwagi,
and
K.Igarashi
(2008).
Binding of spermine and ifenprodil to a purified, soluble regulatory domain of the N-methyl-D-aspartate receptor.
|
| |
J Neurochem,
107,
1566-1577.
|
|
|
|
|
|
|
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:
|
|
|
|
|
|
|
|
A.J.Plested,
and
M.L.Mayer
(2007).
Structure and mechanism of kainate receptor modulation by anions.
|
| |
Neuron,
53,
829-841.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
B.G.Kornreich,
L.Niu,
M.S.Roberson,
and
R.E.Oswald
(2007).
Identification of C-terminal domain residues involved in protein kinase A-mediated potentiation of kainate receptor subtype 6.
|
| |
Neuroscience,
146,
1158-1168.
|
|
|
|
|
|
|
D.L.Minor
(2007).
The neurobiologist's guide to structural biology: a primer on why macromolecular structure matters and how to evaluate structural data.
|
| |
Neuron,
54,
511-533.
|
|
|
|
|
|
|
H.Hald,
P.Naur,
D.S.Pickering,
D.Sprogøe,
U.Madsen,
D.B.Timmermann,
P.K.Ahring,
T.Liljefors,
A.Schousboe,
J.Egebjerg,
M.Gajhede,
and
J.S.Kastrup
(2007).
Partial agonism and antagonism of the ionotropic glutamate receptor iGLuR5: structures of the ligand-binding core in complex with domoic acid and 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid.
|
| |
J Biol Chem,
282,
25726-25736.
|
|
|
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.
|
|
|
|
|
|
|
J.M.Amiel,
and
S.J.Mathew
(2007).
Glutamate and anxiety disorders.
|
| |
Curr Psychiatry Rep,
9,
278-283.
|
|
|
|
|
|
|
K.A.Mankiewicz,
and
V.Jayaraman
(2007).
Glutamate receptors as seen by light: spectroscopic studies of structure-function relationships.
|
| |
Braz J Med Biol Res,
40,
1419-1427.
|
|
|
|
|
|
|
W.Maier,
R.Schemm,
C.Grewer,
and
B.Laube
(2007).
Disruption of interdomain interactions in the glutamate binding pocket affects differentially agonist affinity and efficacy of N-methyl-D-aspartate receptor activation.
|
| |
J Biol Chem,
282,
1863-1872.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
D.J.Wyllie,
A.R.Johnston,
D.Lipscombe,
and
P.E.Chen
(2006).
Single-channel analysis of a point mutation of a conserved serine residue in the S2 ligand-binding domain of the NR2A NMDA receptor subunit.
|
| |
J Physiol,
574,
477-489.
|
|
|
|
|
|
|
I.Huvent,
H.Belrhali,
R.Antoine,
C.Bompard,
C.Locht,
F.Jacob-Dubuisson,
and
V.Villeret
(2006).
Structural analysis of Bordetella pertussis BugE solute receptor in a bound conformation.
|
| |
Acta Crystallogr D Biol Crystallogr,
62,
1375-1381.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.A.Roberts,
and
R.J.Evans
(2006).
Contribution of conserved polar glutamine, asparagine and threonine residues and glycosylation to agonist action at human P2X1 receptors for ATP.
|
| |
J Neurochem,
96,
843-852.
|
|
|
|
|
|
|
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.L.Mayer
(2006).
Glutamate receptors at atomic resolution.
|
| |
Nature,
440,
456-462.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
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
