1T3E: Structural Basis Of Dynamic Glycine Receptor Clustering

Gephyrin is a bi-functional modular protein involved in molybdenum cofactor biosynthesis and in postsynaptic clustering of inhibitory glycine receptors (GlyRs). Here, we show that full-length gephyrin is a trimer and that its proteolysis in vitro causes the spontaneous dimerization of its C-terminal region (gephyrin-E), which binds a GlyR beta-subunit-derived peptide with high and low affinity. The crystal structure of the tetra-domain gephyrin-E in complex with the beta-peptide bound to domain IV indicates how membrane-embedded GlyRs may interact with subsynaptic gephyrin. In vitro, trimeric full-length gephyrin forms a network upon lowering the pH, and this process can be reversed to produce stable full-length dimeric gephyrin. Our data suggest a mechanism by which induced conformational transitions of trimeric gephyrin may generate a reversible postsynaptic scaffold for GlyR recruitment, which allows for dynamic receptor movement in and out of postsynaptic GlyR clusters, and thus for synaptic plasticity.
PDB ID: 1T3EDownload
MMDB ID: 28633
PDB Deposition Date: 2004/4/26
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 3.25  Å
Source Organism:
Similar Structures:
Biological Unit for 1T3E: trimeric; determined by author and by software (PQS)
Molecular Components in 1T3E
Label Count Molecule
Proteins (3 molecules)
Gephyrin(Gene symbol: Gphn)
Molecule annotation
49-mer Fragment of Glycine Receptor Beta Chain(Gene symbol: Glrb)
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB