1T3E

Structural basis of dynamic glycine receptor clustering

Summary for 1T3E

• Entry DOI: 10.2210/pdb1t3e/pdb
• Descriptor: Gephyrin, 49-mer fragment of Glycine receptor beta chain, SULFATE ION (3 entities in total)
• Functional Keywords: alfa-beta, structural protein-signaling protein complex, structural protein/signaling protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell junction, synapse: Q03555; Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P20781
• Total number of polymer chains: 3
• Total formula weight: 97792.77

Authors

Sola, M.,Bavro, V.N.,Timmins, J.,Franz, T.,Ricard-Blum, S.,Schoehn, G.,Ruigrok, R.W.H.,Paarmann, I.,Saiyed, T.,O'Sullivan, G.A. (deposition date: 2004-04-26, release date: 2004-07-27, Last modification date: 2024-04-03)

Primary citation

Sola, M.,Bavro, V.N.,Timmins, J.,Franz, T.,Ricard-Blum, S.,Schoehn, G.,Ruigrok, R.W.H.,Paarmann, I.,Saiyed, T.,O'Sullivan, G.A.,Schmitt, B.,Betz, H.,Weissenhorn, W.
Structural basis of dynamic glycine receptor clustering by gephyrin
Embo J., 23:2510-2519, 2004

PubMed Abstract: 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.

PubMed: 15201864
DOI: 10.1038/sj.emboj.7600256

Experimental method

X-RAY DIFFRACTION (3.25 Å)