8XTY

Structure of human VAChT in complex with vesamicol

これはPDB形式変換不可エントリーです。

8XTY の概要

• エントリーDOI: 10.2210/pdb8xty/pdb
• EMDBエントリー: 38653
• 分子名称: Vesicular acetylcholine transporter,Green fluorescent protein,antibody, vesamicol (2 entities in total)
• 機能のキーワード: transporter, membrane protein, transport protein, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 92203.81

構造登録者

Zhao, Y.,Ma, Q.,Dong, Y.,Meng, Y. (登録日: 2024-01-12, 公開日: 2024-12-25, 最終更新日: 2025-07-16)

主引用文献

Ma, Q.,Ma, K.,Dong, Y.,Meng, Y.,Zhao, J.,Li, R.,Bai, Q.,Wu, D.,Jiang, D.,Sun, J.,Zhao, Y.
Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT.
Nat.Struct.Mol.Biol., 32:818-827, 2025

PubMed Abstract: The vesicular acetylcholine transporter (VAChT) has a pivotal role in packaging and transporting acetylcholine for exocytotic release, serving as a vital component of cholinergic neurotransmission. Dysregulation of its function can result in neurological disorders. It also serves as a target for developing radiotracers to quantify cholinergic neuron deficits in neurodegenerative conditions. Here we unveil the cryo-electron microscopy structures of human VAChT in its apo state, the substrate acetylcholine-bound state and the inhibitor vesamicol-bound state. These structures assume a lumen-facing conformation, offering a clear depiction of architecture of VAChT. The acetylcholine-bound structure provides a detailed understanding of how VAChT recognizes its substrate, shedding light on the coupling mechanism of protonation and substrate binding. Meanwhile, the vesamicol-bound structure reveals the binding mode of vesamicol to VAChT, laying the structural foundation for the design of the next generation of radioligands targeting VAChT.

PubMed: 39806024
DOI: 10.1038/s41594-024-01462-9

実験手法

ELECTRON MICROSCOPY (2.7 Å)