8CE4

Human alpha7 nicotinic receptor in complex with the E3 nanobody

8CE4 の概要

• エントリーDOI: 10.2210/pdb8ce4/pdb
• EMDBエントリー: 16598
• 分子名称: Neuronal acetylcholine receptor subunit alpha-7, Nanobody E3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: ion channel nanobody nicotinic acetylcholine receptor, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 303289.78

構造登録者

Prevost, M.S.,Barilone, N.,Dejean de la Batie, G.,Pons, S.,Ayme, G.,England, P.,Gielen, M.,Bontems, F.,Pehau-Arnaudet, G.,Maskos, U.,Lafaye, P.,Corringer, P.-J. (登録日: 2023-02-01, 公開日: 2023-10-11, 最終更新日: 2025-07-09)

主引用文献

Prevost, M.S.,Barilone, N.,Dejean de la Batie, G.,Pons, S.,Ayme, G.,England, P.,Gielen, M.,Bontems, F.,Pehau-Arnaudet, G.,Maskos, U.,Lafaye, P.,Corringer, P.J.
An original potentiating mechanism revealed by the cryo-EM structures of the human alpha 7 nicotinic receptor in complex with nanobodies.
Nat Commun, 14:5964-5964, 2023

PubMed Abstract: The human α7 nicotinic receptor is a pentameric channel mediating cellular and neuronal communication. It has attracted considerable interest in designing ligands for the treatment of neurological and psychiatric disorders. To develop a novel class of α7 ligands, we recently generated two nanobodies named E3 and C4, acting as positive allosteric modulator and silent allosteric ligand, respectively. Here, we solved the cryo-electron microscopy structures of the nanobody-receptor complexes. E3 and C4 bind to a common epitope involving two subunits at the apex of the receptor. They form by themselves a symmetric pentameric assembly that extends the extracellular domain. Unlike C4, the binding of E3 drives an agonist-bound conformation of the extracellular domain in the absence of an orthosteric agonist, and mutational analysis shows a key contribution of an N-linked sugar moiety in mediating E3 potentiation. The nanobody E3, by remotely controlling the global allosteric conformation of the receptor, implements an original mechanism of regulation that opens new avenues for drug design.

PubMed: 37749098
DOI: 10.1038/s41467-023-41734-4

実験手法

ELECTRON MICROSCOPY (2.7 Å)