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Title: Deciphering the Structural Framework of Glycine Receptor Anchoring by Gephyrin

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 Angstroms 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.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914309
Report Number(s):
BNL-78877-2007-JA
Journal ID: ISSN 0261-4189; EMJODG; TRN: US200809%%166
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: EMBO J.; Journal Volume: 25
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; BRAIN; CRYSTAL STRUCTURE; DIMERS; FASTENING; GLYCINE; IN VITRO; IN VIVO; MONOMERS; MUTAGENESIS; SPINAL CORD; national synchrotron light source

Citation Formats

Kim,E., Schrader, N., Smolinsky, B., Bedet, C., Vannier, C., Schwartz, G., and Schindelin, H. Deciphering the Structural Framework of Glycine Receptor Anchoring by Gephyrin. United States: N. p., 2006. Web. doi:10.1038/sj.emboj.7601029.
Kim,E., Schrader, N., Smolinsky, B., Bedet, C., Vannier, C., Schwartz, G., & Schindelin, H. Deciphering the Structural Framework of Glycine Receptor Anchoring by Gephyrin. United States. doi:10.1038/sj.emboj.7601029.
Kim,E., Schrader, N., Smolinsky, B., Bedet, C., Vannier, C., Schwartz, G., and Schindelin, H. Sun . "Deciphering the Structural Framework of Glycine Receptor Anchoring by Gephyrin". United States. doi:10.1038/sj.emboj.7601029.
@article{osti_914309,
title = {Deciphering the Structural Framework of Glycine Receptor Anchoring by Gephyrin},
author = {Kim,E. and Schrader, N. and Smolinsky, B. and Bedet, C. and Vannier, C. and Schwartz, G. and Schindelin, H.},
abstractNote = {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 Angstroms 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.},
doi = {10.1038/sj.emboj.7601029},
journal = {EMBO J.},
number = ,
volume = 25,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}