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EMBO J. 2006 Mar 22;25(6):1385-95. Epub 2006 Mar 2.

Deciphering the structural framework of glycine receptor anchoring by gephyrin.

Author information

1
Department of Biochemistry, Center for Structural Biology, State University of New York, Stony Brook, NY 11794-5115, USA.

Abstract

Glycine is the major inhibitory neurotransmitter in the spinal cord and brain stem. Gephyrin is required to achieve a high concentration of glycine receptors (GlyRs) in the postsynaptic membrane, which is crucial for efficient glycinergic signal transduction. The interaction between gephyrin and the GlyR involves the E-domain of gephyrin and a cytoplasmic loop located between transmembrane segments three and four of the GlyR beta subunit. Here, we present crystal structures of the gephyrin E-domain with and without the GlyR beta-loop at 2.4 and 2.7 A resolutions, respectively. The GlyR beta-loop is bound in a symmetric 'key and lock' fashion to each E-domain monomer in a pocket adjacent to the dimer interface. Structure-guided mutagenesis followed by in vitro binding and in vivo colocalization assays demonstrate that a hydrophobic interaction formed by Phe 330 of gephyrin and Phe 398 and Ile 400 of the GlyR beta-loop is crucial for binding.

PMID:
16511563
PMCID:
PMC1422172
DOI:
10.1038/sj.emboj.7601029
[Indexed for MEDLINE]
Free PMC Article

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