4TK2

Geph E in complex with a GABA receptor alpha3 subunit derived peptide in space group P61

4TK2 の概要

• エントリーDOI: 10.2210/pdb4tk2/pdb
• 関連するPDBエントリー: 2FTS 2FU3 4PD1 4PDO 4TK1 4TK3 4TK4
• 分子名称: Gephyrin, Gamma-aminobutyric acid receptor subunit alpha-3 (2 entities in total)
• 機能のキーワード: scaffolding protein, neurotransmitter receptor anchoring, molybdenum co factor biosynthesis, structural protein, biosynthetic protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93781.57

構造登録者

Kasaragod, V.B.,Maric, H.M.,Schindelin, H. (登録日: 2014-05-25, 公開日: 2014-12-24, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (4.1 Å)