3U93

Crystal structure of the GluK3 ligand binding domain complex with glutamate and zinc: P2221 form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface.

Veran, J.Kumar, J.Pinheiro, P.S.Athane, A.Mayer, M.L.Perrais, D.Mulle, C.

(2012) Neuron 76: 565-578

  • DOI: https://doi.org/10.1016/j.neuron.2012.08.027
  • Primary Citation of Related Structures:  
    3U92, 3U93, 3U94

  • PubMed Abstract: 

    Kainate receptors (KARs) play a key role in the regulation of synaptic networks. Here, we show that zinc, a cation released at a subset of glutamatergic synapses, potentiates glutamate currents mediated by homomeric and heteromeric KARs containing GluK3 at 10-100 μM concentrations, whereas it inhibits other KAR subtypes. Potentiation of GluK3 currents is mainly due to reduced desensitization, as shown by kinetic analysis and desensitization mutants. Crystallographic and mutation analyses revealed that a specific zinc binding site is formed at the base of the ligand binding domain (LBD) dimer interface by a GluK3-specific aspartate (Asp759), together with two conserved residues, His762 and Asp730, the latter located on the partner subunit. In addition, we propose that tetrameric GluK2/GluK3 receptors are likely assembled as pairs of heterodimeric LBDs. Therefore, zinc binding stabilizes the labile GluK3 dimer interface, slows desensitization, and potentiates currents, providing a mechanism for KAR potentiation at glutamatergic synapses.


  • Organizational Affiliation

    University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutamate receptor, ionotropic kainate 3
A, B
257Rattus norvegicusMutation(s): 0 
Gene Names: GRIK3
UniProt
Find proteins for P42264 (Rattus norvegicus)
Explore P42264 
Go to UniProtKB:  P42264
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP42264
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GLU
Query on GLU

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
GLUTAMIC ACID
C5 H9 N O4
WHUUTDBJXJRKMK-VKHMYHEASA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B],
G [auth B],
H [auth B],
I [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
J [auth B],
K [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
GLU PDBBind:  3U93 Ki: 494 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 130.401α = 90
b = 55.457β = 90
c = 88.861γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-26
    Type: Initial release
  • Version 1.1: 2012-12-19
    Changes: Database references
  • Version 1.2: 2015-08-12
    Changes: Other
  • Version 1.3: 2017-08-09
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description