4TK3

Geph E in complex with a GABA receptor alpha3 derived double mutant peptide in spacegroup P21212

Summary for 4TK3

• Entry DOI: 10.2210/pdb4tk3/pdb
• Related: 4TK1 4TK2 4TK4
• Descriptor: Gephyrin, Gamma-aminobutyric acid receptor subunit alpha-3 (3 entities in total)
• Functional Keywords: scaffolding protein, neurotransmitter receptor anchoring, molybdenum co factor bio synthesis, structural protein, biosynthetic protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 4
• Total formula weight: 93751.63

Authors

Kasaragod, V.B.,Maric, H.M.,Schindelin, H. (deposition date: 2014-05-25, release date: 2014-12-24, Last modification date: 2023-09-27)

Primary citation

Maric, H.M.,Kasaragod, V.B.,Hausrat, T.J.,Kneussel, M.,Tretter, V.,Strmgaard, K.,Schindelin, H.
Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin.
Nat Commun, 5:5767-5767, 2014

PubMed Abstract: γ-Aminobutyric acid type A and glycine receptors (GABA(A)Rs, GlyRs) are the major inhibitory neurotransmitter receptors and contribute to many synaptic functions, dysfunctions and human diseases. GABA(A)Rs are important drug targets regulated by direct interactions with the scaffolding protein gephyrin. Here we deduce the molecular basis of this interaction by chemical, biophysical and structural studies of the gephyrin-GABA(A)R α3 complex, revealing that the N-terminal region of the α3 peptide occupies the same binding site as the GlyR β subunit, whereas the C-terminal moiety, which is conserved among all synaptic GABA(A)R α subunits, engages in unique interactions. Thermodynamic dissections of the gephyrin-receptor interactions identify two residues as primary determinants for gephyrin's subunit preference. This first structural evidence for the gephyrin-mediated synaptic accumulation of GABA(A)Rs offers a framework for future investigations into the regulation of inhibitory synaptic strength and for the development of mechanistically and therapeutically relevant compounds targeting the gephyrin-GABA(A)R interaction.

PubMed: 25531214
DOI: 10.1038/ncomms6767

Experimental method

X-RAY DIFFRACTION (2.7 Å)