8P1H

Crystal structure of the chimera of human 14-3-3 zeta and phosphorylated cytoplasmic loop fragment of the alpha7 acetylcholine receptor

8P1H の概要

• エントリーDOI: 10.2210/pdb8p1h/pdb
• 分子名称: Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta,Neuronal acetylcholine receptor subunit alpha-7, 1,2-ETHANEDIOL, AZIDE ION, ... (6 entities in total)
• 機能のキーワード: 14-3-3, acetylcholine receptor, protein binding, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56235.12

構造登録者

Boyko, K.M.,Kapitonova, A.A.,Tugaeva, K.V.,Varfolomeeva, L.A.,Lyukmanova, E.N.,Sluchanko, N.N. (登録日: 2023-05-12, 公開日: 2023-10-18, 最終更新日: 2024-11-13)

主引用文献

Sluchanko, N.N.,Kapitonova, A.A.,Shulepko, M.A.,Kukushkin, I.D.,Kulbatskii, D.S.,Tugaeva, K.V.,Varfolomeeva, L.A.,Minyaev, M.E.,Boyko, K.M.,Popov, V.O.,Kirpichnikov, M.P.,Lyukmanova, E.N.
Crystal structure reveals canonical recognition of the phosphorylated cytoplasmic loop of human alpha7 nicotinic acetylcholine receptor by 14-3-3 protein.
Biochem.Biophys.Res.Commun., 682:91-96, 2023

PubMed Abstract: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five homologous subunits. The homopentameric α7-nAChR, abundantly expressed in the brain, is involved in the regulation of the neuronal plasticity and memory and undergoes phosphorylation by protein kinase A (PKA). Here, we extracted native α7-nAChR from murine brain, validated its assembly by cryo-EM and showed that phosphorylation by PKA in vitro enables its interaction with the abundant human brain protein 14-3-3ζ. Bioinformatic analysis narrowed the putative 14-3-3-binding site down to the fragment of the intracellular loop (ICL) containing Ser365 (QRRCSLASVEMS), known to be phosphorylated in vivo. We reconstructed the 14-3-3ζ/ICL peptide complex and determined its structure by X-ray crystallography, which confirmed the Ser365 phosphorylation-dependent canonical recognition of the ICL by 14-3-3. A common mechanism of nAChRs' regulation by ICL phosphorylation and 14-3-3 binding that potentially affects nAChR activity, stoichiometry, and surface expression is suggested.

PubMed: 37804592
DOI: 10.1016/j.bbrc.2023.09.086

実験手法

X-RAY DIFFRACTION (1.95 Å)