2PR9

Mu2 adaptin subunit (AP50) of AP2 adaptor (second domain), complexed with GABAA receptor-gamma2 subunit-derived internalization peptide DEEYGYECL

2PR9 の概要

• エントリーDOI: 10.2210/pdb2pr9/pdb
• 関連するPDBエントリー: 1BW8
• 分子名称: AP-2 complex subunit mu-1, GABA(A) receptor subunit gamma-2 peptide (3 entities in total)
• 機能のキーワード: endocytosis, adaptor, internalization peptide complex, inhibitory neurotransmitter receptor
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cell membrane (By similarity): P84092; Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P18508
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35336.07

構造登録者

Vahedi-Faridi, A.,Haucke, V.,Kittler, J.T.,Kukhtina, V.,Moss, S.J.,Saenger, W.,Chen, G.-J.,Tretter, V.,Smith, K.,Yan, Z.,McAinsh, K.,Arancibia-Carcamo, L. (登録日: 2007-05-04, 公開日: 2008-03-18, 最終更新日: 2023-08-30)

主引用文献

Kittler, J.T.,Chen, G.,Kukhtina, V.,Vahedi-Faridi, A.,Gu, Z.,Tretter, V.,Smith, K.R.,McAinsh, K.,Arancibia-Carcamo, I.L.,Saenger, W.,Haucke, V.,Yan, Z.,Moss, S.J.
Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor gamma2 subunit.
Proc.Natl.Acad.Sci.Usa, 105:3616-3621, 2008

PubMed Abstract: The regulation of the number of gamma2-subunit-containing GABA(A) receptors (GABA(A)Rs) present at synapses is critical for correct synaptic inhibition and animal behavior. This regulation occurs, in part, by the controlled removal of receptors from the membrane in clathrin-coated vesicles, but it remains unclear how clathrin recruitment to surface gamma2-subunit-containing GABA(A)Rs is regulated. Here, we identify a gamma2-subunit-specific Yxxvarphi-type-binding motif for the clathrin adaptor protein, AP2, which is located within a site for gamma2-subunit tyrosine phosphorylation. Blocking GABA(A)R-AP2 interactions via this motif increases synaptic responses within minutes. Crystallographic and biochemical studies reveal that phosphorylation of the Yxxvarphi motif inhibits AP2 binding, leading to increased surface receptor number. In addition, the crystal structure provides an explanation for the high affinity of this motif for AP2 and suggests that gamma2-subunit-containing heteromeric GABA(A)Rs may be internalized as dimers or multimers. These data define a mechanism for tyrosine kinase regulation of GABA(A)R surface levels and synaptic inhibition.

PubMed: 18305175
DOI: 10.1073/pnas.0707920105

実験手法

X-RAY DIFFRACTION (2.51 Å)