8J76

Human high-affinity choline transporter CHT1 in the inward-facing apo-open conformation

8J76 の概要

• エントリーDOI: 10.2210/pdb8j76/pdb
• EMDBエントリー: 36029
• 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 (2 entities in total)
• 機能のキーワード: cht1, slc5a7, high affinity choline transporter, choline transporter, membrane 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: 63825.69

構造登録者

Gao, Y.,Qiu, Y.,Zhao, Y. (登録日: 2023-04-27, 公開日: 2024-04-10, 最終更新日: 2025-07-23)

主引用文献

Qiu, Y.,Gao, Y.,Huang, B.,Bai, Q.,Zhao, Y.
Transport mechanism of presynaptic high-affinity choline uptake by CHT1.
Nat.Struct.Mol.Biol., 31:701-709, 2024

PubMed Abstract: Choline is a vital nutrient and a precursor for the biosynthesis of essential metabolites, including acetylcholine (ACh), that play a central role in fetal development, especially in the brain. In cholinergic neurons, the high-affinity choline transporter (CHT1) provides an extraordinarily efficient reuptake mechanism to reutilize choline derived from intrasynaptical ACh hydrolysis and maintain ACh synthesis in the presynapse. Here, we determined structures of human CHT1 in three discrete states: the outward-facing state bound with the competitive inhibitor hemicholinium-3 (HC-3); the inward-facing occluded state bound with the substrate choline; and the inward-facing apo open state. Our structures and functional characterizations elucidate how the inhibitor and substrate are recognized. Moreover, our findings shed light on conformational changes when transitioning from an outward-facing to an inward-facing state and establish a framework for understanding the transport cycle, which relies on the stabilization of the outward-facing state by a short intracellular helix, IH1.

PubMed: 38589607
DOI: 10.1038/s41594-024-01259-w

実験手法

ELECTRON MICROSCOPY (3.7 Å)