4TK1

Geph E in complex with a GABA receptor alpha3 subunit derived peptide in space group P21212


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin.

Maric, H.M.Kasaragod, V.B.Hausrat, T.J.Kneussel, M.Tretter, V.Strmgaard, K.Schindelin, H.

(2014) Nat Commun 5: 5767-5767

  • DOI: https://doi.org/10.1038/ncomms6767
  • Primary Citation of Related Structures:  
    4TK1, 4TK2, 4TK3, 4TK4

  • PubMed Abstract: 

    γ-Aminobutyric acid type A and glycine receptors (GABA(A)Rs, GlyRs) are the major inhibitory neurotransmitter receptors and contribute to many synaptic functions, dysfunctions and human diseases. GABA(A)Rs are important drug targets regulated by direct interactions with the scaffolding protein gephyrin. Here we deduce the molecular basis of this interaction by chemical, biophysical and structural studies of the gephyrin-GABA(A)R α3 complex, revealing that the N-terminal region of the α3 peptide occupies the same binding site as the GlyR β subunit, whereas the C-terminal moiety, which is conserved among all synaptic GABA(A)R α subunits, engages in unique interactions. Thermodynamic dissections of the gephyrin-receptor interactions identify two residues as primary determinants for gephyrin's subunit preference. This first structural evidence for the gephyrin-mediated synaptic accumulation of GABA(A)Rs offers a framework for future investigations into the regulation of inhibitory synaptic strength and for the development of mechanistically and therapeutically relevant compounds targeting the gephyrin-GABA(A)R interaction.


  • Organizational Affiliation

    1] Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Straße 2, Building D15, D-97080 Würzburg, Germany [2] Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Gephyrin
A, B
419Rattus norvegicusMutation(s): 0 
Gene Names: GphnGph
EC: 2.7.7.75 (PDB Primary Data), 2.10.1.1 (PDB Primary Data)
UniProt
Find proteins for Q03555 (Rattus norvegicus)
Explore Q03555 
Go to UniProtKB:  Q03555
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ03555
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Gamma-aminobutyric acid receptor subunit alpha-3
C, D
11Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for P20236 (Rattus norvegicus)
Explore P20236 
Go to UniProtKB:  P20236
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20236
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.218 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.439α = 90
b = 157.695β = 90
c = 51.018γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research Foundation (DFG)GermanySchi 425/ 8-1

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-24
    Type: Initial release
  • Version 1.1: 2015-02-04
    Changes: Database references
  • Version 1.2: 2017-09-27
    Changes: Author supporting evidence, Derived calculations, Other, Source and taxonomy
  • Version 1.3: 2020-01-08
    Changes: Author supporting evidence
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description