Structural basis of dynamic glycine receptor clustering by gephyrin

Autor: Bertram Schmitt, Vassiliy N. Bavro, Taslimarif Saiyed, Maria Solà, Joanna Timmins, Guy Schoehn, Gregory A. O'Sullivan, Thomas Franz, Heinrich Betz, Ingo Paarmann, Rob W.H. Ruigrok, Sylvie Ricard-Blum, Winfried Weissenhorn
Přispěvatelé: Deleage, Gilbert
Rok vydání: 2004
Předmět:
Models
Molecular
Protein Conformation
Coenzymes
Crystallography
X-Ray
Mass Spectrometry
Receptors
Glycine
Protein structure
Postsynaptic potential
Trypsin
Glycine receptor
Glycine receptor clustering
biology
Sulfates
Hydrolysis
Pteridines
General Neuroscience
Hydrogen-Ion Concentration
Solutions
Biochemistry
Chromatography
Gel
Dimerization
Glycine inhibitory receptor
Protein Binding
Inhibitory postsynaptic potential
Gephyrin E-domain
Synaptic plasticity
Article
General Biochemistry
Genetics and Molecular Biology
Receptor clustering
Metalloproteins
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
Molecular Biology
Binding Sites
General Immunology and Microbiology
Gephyrin
Membrane Proteins
Surface Plasmon Resonance
Peptide Fragments
Protein Structure
Tertiary
Rats
Protein Subunits
Models
Chemical
Synapses
biology.protein
Biophysics
Carrier Proteins
Molybdenum Cofactors
Collybistin
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1460-2075
0261-4189
DOI: 10.1038/sj.emboj.7600256
Popis: Maria Solà et al.
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.
This work was supported by EMBL (WW), Deutsche Forschungsgemeinschaft (SFB 628) and ‘Fonds der Chemischen Industrie’ (HB). VB was supported by a predoctoral fellowship from the ‘Louis-Jeantet Fondation de Medicine’ and MS and GAO’S were both supported by a Marie Curie fellowship from the European Union
Databáze: OpenAIRE
Externí odkaz: