3GSL

Crystal structure of PSD-95 tandem PDZ domains 1 and 2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.221 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization.

Sainlos, M.Tigaret, C.Poujol, C.Olivier, N.B.Bard, L.Breillat, C.Thiolon, K.Choquet, D.Imperiali, B.

(2011) Nat Chem Biol 7: 81-91

  • DOI: https://doi.org/10.1038/nchembio.498
  • Primary Citation of Related Structures:  
    3GSL

  • PubMed Abstract: 

    The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes.


  • Organizational Affiliation

    Department of Chemistry and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Disks large homolog 4
A, B
196Rattus norvegicusMutation(s): 0 
Gene Names: Dlg4Dlgh4PSD-95Psd95
UniProt
Find proteins for P31016 (Rattus norvegicus)
Explore P31016 
Go to UniProtKB:  P31016
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP31016
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.221 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.244α = 90
b = 62.511β = 99.25
c = 59.342γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
REFMACrefinement
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: 2010-09-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Refinement description