8Y94

Structure of Apo human norepinephrine transporter NET

8Y94 の概要

• エントリーDOI: 10.2210/pdb8y94/pdb
• EMDBエントリー: 39069
• 分子名称: Sodium-dependent noradrenaline transporter (1 entity in total)
• 機能のキーワード: neurotransmitter, transporters, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 138773.09

構造登録者

Zhang, H.,Xu, H.E.,Jiang, Y. (登録日: 2024-02-06, 公開日: 2024-05-29, 最終更新日: 2024-07-03)

主引用文献

Zhang, H.,Yin, Y.L.,Dai, A.,Zhang, T.,Zhang, C.,Wu, C.,Hu, W.,He, X.,Pan, B.,Jin, S.,Yuan, Q.,Wang, M.W.,Yang, D.,Xu, H.E.,Jiang, Y.
Dimerization and antidepressant recognition at noradrenaline transporter.
Nature, 630:247-254, 2024

PubMed Abstract: The noradrenaline transporter has a pivotal role in regulating neurotransmitter balance and is crucial for normal physiology and neurobiology. Dysfunction of noradrenaline transporter has been implicated in numerous neuropsychiatric diseases, including depression and attention deficit hyperactivity disorder. Here we report cryo-electron microscopy structures of noradrenaline transporter in apo and substrate-bound forms, and as complexes with six antidepressants. The structures reveal a noradrenaline transporter dimer interface that is mediated predominantly by cholesterol and lipid molecules. The substrate noradrenaline binds deep in the central binding pocket, and its amine group interacts with a conserved aspartate residue. Our structures also provide insight into antidepressant recognition and monoamine transporter selectivity. Together, these findings advance our understanding of noradrenaline transporter regulation and inhibition, and provide templates for designing improved antidepressants to treat neuropsychiatric disorders.

PubMed: 38750358
DOI: 10.1038/s41586-024-07437-6

実験手法

ELECTRON MICROSCOPY (3.29 Å)