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PDBsum entry 3kfm
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Transport protein
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PDB id
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3kfm
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Contents |
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* Residue conservation analysis
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PDB id:
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Transport protein
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Title:
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Crystal structure of the glua4 ligand-binding domain l651v mutant in complex with kainate
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Structure:
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Glutamate receptor 4. Chain: a. Fragment: ligand binding domain. Synonym: glur-4, glur4, glur-d, glutamate receptor ionotropic, ampa 4, ampa-selective glutamate receptor 4. Engineered: yes. Mutation: yes
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Source:
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Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Strain: sprague-dawley. Gene: glur4, gria4. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.20Å
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R-factor:
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0.190
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R-free:
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0.274
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Authors:
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A.Gill,D.R.Madden
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Key ref:
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A.Birdsey-Benson
et al.
(2010).
Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors.
J Neurosci,
30,
1463-1470.
PubMed id:
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Date:
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27-Oct-09
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Release date:
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09-Feb-10
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PROCHECK
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Headers
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References
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P19493
(GRIA4_RAT) -
Glutamate receptor 4 from Rattus norvegicus
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Seq:
Struc:
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902 a.a.
257 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 9 residue positions (black
crosses)
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J Neurosci
30:1463-1470
(2010)
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PubMed id:
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Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors.
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A.Birdsey-Benson,
A.Gill,
L.P.Henderson,
D.R.Madden.
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ABSTRACT
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AMPA receptors (AMPARs) are tetrameric ligand-gated ion channels that couple the
energy of glutamate binding to the opening of a transmembrane channel.
Crystallographic and electrophysiological analysis of AMPARs has suggested a
coupling between (1) cleft closure in the bilobate ligand-binding domain (LBD),
(2) the resulting separation of transmembrane helix attachment points across
subunit dimers, and (3) agonist efficacy. In general, more efficacious agonists
induce greater degrees of cleft closure and transmembrane separation than
partial agonists. Several apparent violations of the cleft-closure/efficacy
paradigm have emerged, although in all cases, intradimer separation remains as
the driving force for channel opening. Here, we examine the structural basis of
partial agonism in GluA4 AMPARs. We find that the L651V substitution enhances
the relative efficacy of kainate without increasing either LBD cleft closure or
transmembrane separation. Instead, the conformational change relative to the
wild-type:kainate complex involves a twisting motion with the efficacy
contribution opposite from that expected based on previous analyses. As a
result, channel opening may involve transmembrane rearrangements with a
significant rotational component. Furthermore, a two-dimensional analysis of
agonist-induced GluA2 LBD motions suggests that efficacy is not a linearly
varying function of lobe 2 displacement vectors, but is rather determined by
specific conformational requirements of the transmembrane domains.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Y.Lau,
and
B.Roux
(2011).
The hidden energetics of ligand binding and activation in a glutamate receptor.
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Nat Struct Mol Biol,
18,
283-287.
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C.F.Landes,
A.Rambhadran,
J.N.Taylor,
F.Salatan,
and
V.Jayaraman
(2011).
Structural landscape of isolated agonist-binding domains from single AMPA receptors.
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Nat Chem Biol,
7,
168-173.
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D.Stroebel,
S.Carvalho,
and
P.Paoletti
(2011).
Functional evidence for a twisted conformation of the NMDA receptor GluN2A subunit N-terminal domain.
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Neuropharmacology,
60,
151-158.
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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.
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Links
