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PDBsum entry 2i3w
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protein ligands Protein-protein interface(s) links
Membrane protein PDB id
2i3w

 

 

 

 

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Contents
Protein chains
258 a.a. *
Ligands
GLU ×2
Waters ×200
* Residue conservation analysis
PDB id:
2i3w
Name: Membrane protein
Title: Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor: structure of s729c mutant
Structure: Glutamate receptor subunit 2. Chain: a, b. Fragment: ligand binding core (s1s2j). Synonym: glur-2. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: brain. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.240     R-free:   0.284
Authors: N.Armstrong,J.Jasti,M.Beich-Frandsen,E.Gouaux
Key ref:
N.Armstrong et al. (2006). Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. Cell, 127, 85-97. PubMed id: 17018279 DOI: 10.1016/j.cell.2006.08.037
Date:
21-Aug-06     Release date:   17-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		883 a.a.
258 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 

 
DOI no: 10.1016/j.cell.2006.08.037 Cell 127:85-97 (2006)
PubMed id: 17018279  
 
 
Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor.
N.Armstrong, J.Jasti, M.Beich-Frandsen, E.Gouaux.
 
  ABSTRACT  
 
The canonical conformational states occupied by most ligand-gated ion channels, and many cell-surface receptors, are the resting, activated, and desensitized states. While the resting and activated states of multiple receptors are well characterized, elaboration of the structural properties of the desensitized state, a state that is by definition inactive, has proven difficult. Here we use electrical, chemical, and crystallographic experiments on the AMPA-sensitive GluR2 receptor, defining the conformational rearrangements of the agonist binding cores that occur upon desensitization of this ligand-gated ion channel. These studies demonstrate that desensitization involves the rupture of an extensive interface between domain 1 of 2-fold related glutamate-binding core subunits, compensating for the ca. 21 degrees of domain closure induced by glutamate binding. The rupture of the domain 1 interface allows the ion channel to close and thereby provides a simple explanation to the long-standing question of how agonist binding is decoupled from ion channel gating upon receptor desensitization.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. MTSES Modification of E486C in Closed, Open, and Desensitized States 		Figure 7.
Figure 7. Mechanism of Activation and Desensitization
 
  The above figures are reprinted by permission from Cell Press: Cell (2006, 127, 85-97) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20713069 J.Pøhlsgaard, K.Frydenvang, U.Madsen, and J.S.Kastrup (2011).
Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators.
  Neuropharmacology, 60, 135-150.  
21317871 M.Sukumaran, M.Rossmann, I.Shrivastava, A.Dutta, I.Bahar, and I.H.Greger (2011).
Dynamics and allosteric potential of the AMPA receptor N-terminal domain.
  EMBO J, 30, 972-982.
PDB codes: 3o21 3p3w
20199107 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: 3m3f 3m3k 3m3l
20457909 J.Gonzalez, M.Du, K.Parameshwaran, V.Suppiramaniam, and V.Jayaraman (2010).
Role of dimer interface in activation and desensitization in AMPA receptors.
  Proc Natl Acad Sci U S A, 107, 9891-9896.  
20622973 J.Kalia, and R.T.Raines (2010).
Advances in Bioconjugation.
  Curr Org Chem, 14, 138-147.  
20564790 O.B.Clarke, A.T.Caputo, A.P.Hill, J.I.Vandenberg, B.J.Smith, and J.M.Gulbis (2010).
Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.
  Cell, 141, 1018-1029.
PDB codes: 2wlh 2wli 2wlj 2wlk 2wll 2wlm 2wln 2wlo 2x6a 2x6b 2x6c
21080238 T.Nakagawa (2010).
The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors.
  Mol Neurobiol, 42, 161-184.  
20404149 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.  
19946266 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: 3kg2 3kgc
18687343 A.J.Plested, and M.L.Mayer (2009).
Engineering a high-affinity allosteric binding site for divalent cations in kainate receptors.
  Neuropharmacology, 56, 114-120.  
19776277 A.J.Plested, and M.L.Mayer (2009).
AMPA receptor ligand binding domain mobility revealed by functional cross linking.
  J Neurosci, 29, 11912-11923.  
19617541 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.  
19339989 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: 3g3f 3g3g 3g3h 3g3i 3g3j 3g3k
19481093 D.Schmidt, S.R.Cross, and R.MacKinnon (2009).
A gating model for the archeal voltage-dependent K(+) channel KvAP in DPhPC and POPE:POPG decane lipid bilayers.
  J Mol Biol, 390, 902-912.  
20467570 J.Kalia, and R.T.Raines (2009).
1,9-Bis(2-pyridyl)-1,2,8,9-tetrathia-5-oxanonane.
  Molbank, 2009, M642.  
19176800 K.B.Hansen, P.Naur, N.L.Kurtkaya, A.S.Kristensen, M.Gajhede, J.S.Kastrup, and S.F.Traynelis (2009).
Modulation of the dimer interface at ionotropic glutamate-like receptor delta2 by D-serine and extracellular calcium.
  J Neurosci, 29, 907-917.  
19297335 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: 3gba 3gbb
19544581 M.Du, A.Rambhadran, and V.Jayaraman (2009).
Vibrational spectroscopic investigation of the ligand binding domain of kainate receptors.
  Protein Sci, 18, 1585-1591.  
19146816 M.Morimoto-Tomita, W.Zhang, C.Straub, C.H.Cho, K.S.Kim, J.R.Howe, and S.Tomita (2009).
Autoinactivation of neuronal AMPA receptors via glutamate-regulated TARP interaction.
  Neuron, 61, 101-112.  
19461580 R.Jin, S.K.Singh, S.Gu, H.Furukawa, A.I.Sobolevsky, J.Zhou, Y.Jin, and E.Gouaux (2009).
Crystal structure and association behaviour of the GluR2 amino-terminal domain.
  EMBO J, 28, 1812-1823.
PDB codes: 3h5v 3h5w
19506248 S.M.Schmid, S.Kott, C.Sager, T.Huelsken, and M.Hollmann (2009).
The glutamate receptor subunit delta2 is capable of gating its intrinsic ion channel as revealed by ligand binding domain transplantation.
  Proc Natl Acad Sci U S A, 106, 10320-10325.  
19560629 T.P.Möykkynen, S.K.Coleman, K.Keinänen, D.M.Lovinger, and E.R.Korpi (2009).
Ethanol increases desensitization of recombinant GluR-D AMPA receptor and TARP combinations.
  Alcohol, 43, 277-284.  
18923416 A.C.Penn, S.R.Williams, and I.H.Greger (2008).
Gating motions underlie AMPA receptor secretion from the endoplasmic reticulum.
  EMBO J, 27, 3056-3068.  
18514334 A.D.Milstein, and R.A.Nicoll (2008).
Regulation of AMPA receptor gating and pharmacology by TARP auxiliary subunits.
  Trends Pharmacol Sci, 29, 333-339.  
18549784 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: 3c31 3c32 3c33 3c34 3c35 3c36
18214958 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.  
18759455 J.Gonzalez, A.Rambhadran, M.Du, and V.Jayaraman (2008).
LRET investigations of conformational changes in the ligand binding domain of a functional AMPA receptor.
  Biochemistry, 47, 10027-10032.  
18081322 K.A.Mankiewicz, A.Rambhadran, L.Wathen, and V.Jayaraman (2008).
Chemical interplay in the mechanism of partial agonist activation in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
  Biochemistry, 47, 398-404.  
18367452 K.B.Craven, N.B.Olivier, and W.N.Zagotta (2008).
C-terminal movement during gating in cyclic nucleotide-modulated channels.
  J Biol Chem, 283, 14728-14738.
PDB code: 3bpz
18658129 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.  
18184566 M.Gielen, A.Le Goff, D.Stroebel, J.W.Johnson, J.Neyton, and P.Paoletti (2008).
Structural rearrangements of NR1/NR2A NMDA receptors during allosteric inhibition.
  Neuron, 57, 80-93.  
18387631 M.K.Fenwick, and R.E.Oswald (2008).
NMR spectroscopy of the ligand-binding core of ionotropic glutamate receptor 2 bound to 5-substituted willardiine partial agonists.
  J Mol Biol, 378, 673-685.  
17337449 A.H.Ahmed, A.P.Loh, D.E.Jane, and R.E.Oswald (2007).
Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy.
  J Biol Chem, 282, 12773-12784.  
17359918 A.J.Plested, and M.L.Mayer (2007).
Structure and mechanism of kainate receptor modulation by anions.
  Neuron, 53, 829-841.
PDB code: 2ojt
17937910 A.Y.Lau, and B.Roux (2007).
The free energy landscapes governing conformational changes in a glutamate receptor ligand-binding domain.
  Structure, 15, 1203-1214.  
17202478 H.Augustin, Y.Grosjean, K.Chen, Q.Sheng, and D.E.Featherstone (2007).
Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo.
  J Neurosci, 27, 111-123.  
17629578 I.H.Greger, E.B.Ziff, and A.C.Penn (2007).
Molecular determinants of AMPA receptor subunit assembly.
  Trends Neurosci, 30, 407-416.  
17637801 J.E.Lisman, S.Raghavachari, and R.W.Tsien (2007).
The sequence of events that underlie quantal transmission at central glutamatergic synapses.
  Nat Rev Neurosci, 8, 597-609.  
17208968 N.A.Mitchell, and M.W.Fleck (2007).
Targeting AMPA receptor gating processes with allosteric modulators and mutations.
  Biophys J, 92, 2392-2402.  
17115050 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: 2i0b 2i0c
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.

 

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