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Structural basis of dynamic glycine receptor clustering by gephyrin
Author(s) -
Sola Maria,
Bavro Vassiliy N,
Timmins Joanna,
Franz Thomas,
RicardBlum Sylvie,
Schoehn Guy,
Ruigrok Rob WH,
Paarmann Ingo,
Saiyed Taslimarif,
O'Sullivan Gregory A,
Schmitt Bertram,
Betz Heinrich,
Weissenhorn Winfried
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600256
Subject(s) - gephyrin , glycine receptor , postsynaptic potential , biophysics , trimer , biology , proteolysis , inhibitory postsynaptic potential , microbiology and biotechnology , molybdenum cofactor , biochemistry , glycine , receptor , amino acid , neuroscience , chemistry , mutant , dimer , organic chemistry , gene , enzyme
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 β‐subunit‐derived peptide with high and low affinity. The crystal structure of the tetra‐domain gephyrin‐E in complex with the β‐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.