2FU3

Crystal structure of gephyrin E-domain

Summary for 2FU3

• Entry DOI: 10.2210/pdb2fu3/pdb
• Related: 2FTS
• Descriptor: gephyrin (2 entities in total)
• Functional Keywords: glycine receptor, gephyrin, neuroreceptor anchoring, biosynthetic protein-structural protein complex, biosynthetic protein/structural protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cell junction, synapse : Q03555
• Total number of polymer chains: 2
• Total formula weight: 91304.79

Authors

Kim, E.Y.,Schindelin, H. (deposition date: 2006-01-25, release date: 2006-03-14, Last modification date: 2024-02-14)

Primary citation

Kim, E.Y.,Schrader, N.,Smolinsky, B.,Bedet, C.,Vannier, C.,Schwarz, G.,Schindelin, H.
Deciphering the structural framework of glycine receptor anchoring by gephyrin.
Embo J., 25:1385-1395, 2006

PubMed 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.

PubMed: 16511563
DOI: 10.1038/sj.emboj.7601029

Experimental method

X-RAY DIFFRACTION (2.7 Å)