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EMBO J. 2004 Jul 7;23(13):2510-9. Epub 2004 Jun 17.

Structural basis of dynamic glycine receptor clustering by gephyrin.

Author information

1
European Molecular Biology Laboratory, Grenoble, France.

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.

PMID:
15201864
PMCID:
PMC449768
DOI:
10.1038/sj.emboj.7600256
[Indexed for MEDLINE]
Free PMC Article

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