4PD1: Structure of gephyrin E domain with Glycine-beta receptor peptide

Gephyrin is a major determinant for the accumulation and anchoring of glycine receptors (GlyRs) and the majority of gamma-aminobutyric acid type A receptors (GABAARs) at postsynaptic sites. Here we explored the interaction of gephyrin with a dimeric form of a GlyR beta-subunit receptor-derived peptide. A 2 A crystal structure of the C-terminal domain of gephyrin (GephE) in complex with a 15-residue peptide derived from the GlyR beta-subunit defined the core binding site, which we targeted with the dimeric peptide. Biophysical analyses via differential scanning calorimetry (DSC), thermofluor, and isothermal titration calorimetry (ITC) demonstrated that this dimeric ligand is capable of binding simultaneously to two receptor binding sites and that this multivalency results in a 25-fold enhanced affinity. Our study therefore suggests that the oligomeric state of gephyrin and the number of gephyrin-binding subunits in the pentameric GABAARs and GlyRs together control postsynaptic receptor clustering.
PDB ID: 4PD1Download
MMDB ID: 122731
PDB Deposition Date: 2014/4/17
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 1.975  Å
Source Organism:
Rattus norvegicus
Similar Structures:
Biological Unit for 4PD1: tetrameric; determined by author and by software (PISA)
Molecular Components in 4PD1
Label Count Molecule
Proteins (4 molecules)
Gephyrin(Gene symbol: Gphn)
Molecule annotation
Glycine Receptor Subunit Beta(Gene symbol: Glrb)
Molecule annotation
Chemicals (18 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB