RCSB PDB - 6FQI: GluA2(flop) G724C ligand binding core dimer bound to L-Glutamate (Form B) at 2.91 Angstrom resolution

 6FQI

GluA2(flop) G724C ligand binding core dimer bound to L-Glutamate (Form B) at 2.91 Angstrom resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.91 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 2.2 of the entry. See complete history


Literature

Homomeric GluA2(R) AMPA receptors can conduct when desensitized.

Coombs, I.D.Soto, D.McGee, T.P.Gold, M.G.Farrant, M.Cull-Candy, S.G.

(2019) Nat Commun 10: 4312-4312

  • DOI: https://doi.org/10.1038/s41467-019-12280-9
  • Primary Citation of Related Structures:  
    6FQH, 6FQI, 6FQJ, 6FQK

  • PubMed Abstract: 

    Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors (AMPARs), which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we present evidence that homomeric Q/R-edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits (γ-2, γ-8 or GSG1L), generates large fractional steady-state currents and anomalous current-variance relationships. Our results from fluctuation analysis, single-channel recording, and kinetic modeling, suggest that the steady-state current is mediated predominantly by conducting desensitized receptors. When combined with crystallography this unique functional readout of a hitherto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes.


  • Organizational Affiliation

    Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutamate receptor 2
A, B
264Rattus norvegicusMutation(s): 0 
Gene Names: Gria2Glur2
UniProt
Find proteins for P19491 (Rattus norvegicus)
Explore P19491 
Go to UniProtKB:  P19491
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19491
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.91 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.65α = 90
b = 50.65β = 90
c = 256.29γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PHASERphasing
xia2data reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomMR/J002976/1
Medical Research Council (United Kingdom)United KingdomMR/J012998/1
Wellcome TrustUnited Kingdom086185/Z/08/Z

Revision History  (Full details and data files)

  • Version 1.0: 2019-03-13
    Type: Initial release
  • Version 1.1: 2019-10-02
    Changes: Data collection, Database references
  • Version 2.0: 2023-03-15
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Source and taxonomy, Structure summary
  • Version 2.1: 2024-02-07
    Changes: Data collection, Refinement description
  • Version 2.2: 2024-11-13
    Changes: Structure summary