8ZQO

Human high-affinity choline transporter CHT1 bound to HC-3 under NaCl condition, with sodium and chloride ions coordinated.

8ZQO の概要

• エントリーDOI: 10.2210/pdb8zqo/pdb
• EMDBエントリー: 60386
• 分子名称: High affinity choline transporter 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: transporter, structural protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64321.66

構造登録者

Qiu, Y.,Gao, Y.,Zhao, Y. (登録日: 2024-06-03, 公開日: 2024-12-04, 最終更新日: 2025-07-23)

主引用文献

Qiu, Y.,Gao, Y.,Bai, Q.,Zhao, Y.
Ion coupling and inhibitory mechanisms of the human presynaptic high-affinity choline transporter CHT1.
Structure, 33:321-, 2025

PubMed Abstract: In cholinergic neurons, choline is the precursor of the excitatory neurotransmitter acetylcholine (ACh), which plays a fundamental role in the brain. The high-affinity choline transporter, CHT1, mediates the efficient recycling of choline to facilitate ACh synthesis in the presynapse. Here, we report high-resolution cryoelectron microscopic (cryo-EM) structures of CHT1 in complex with the inhibitors HC-3 and ML352, the substrate choline, and a substrate-free state. Our structures show distinct binding modes of the inhibitors with different chemical structures, revealing their inhibition mechanisms. Additionally, we observed a chloride ion that directly interacts with the substrate choline, thereby stabilizing its binding with CHT1. Two sodium ions, Na2 and Na3, were clearly identified, which we speculate might be involved in substrate binding and conformational transitions, respectively. Our structures provide molecular insights into the coupling mechanism of ion binding with substrate binding and conformational transitions, promoting our understanding of the ion-coupled substrate transport mechanism.

PubMed: 39657660
DOI: 10.1016/j.str.2024.11.009

実験手法

ELECTRON MICROSCOPY (2.8 Å)