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-Structure paper
タイトル | Dimerization and antidepressant recognition at noradrenaline transporter. |
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ジャーナル・号・ページ | Nature, Vol. 630, Issue 8015, Page 247-254, Year 2024 |
掲載日 | 2024年5月15日 |
著者 | Heng Zhang / Yu-Ling Yin / Antao Dai / Tianwei Zhang / Chao Zhang / Canrong Wu / Wen Hu / Xinheng He / Benxun Pan / Sanshan Jin / Qingning Yuan / Ming-Wei Wang / Dehua Yang / H Eric Xu / Yi Jiang / |
PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:38750358 |
手法 | EM (単粒子) |
解像度 | 2.89 - 3.29 Å |
構造データ | EMDB-39064, PDB-8y8z: EMDB-39065, PDB-8y90: EMDB-39066, PDB-8y91: EMDB-39067, PDB-8y92: EMDB-39068, PDB-8y93: EMDB-39069, PDB-8y94: EMDB-39070, PDB-8y95: EMDB-39533, PDB-8yr2: |
化合物 | PDB-1lx3: ChemComp-NA: ChemComp-CL: ChemComp-HOH: PDB-1lx6: PDB-1lx5:
PDB-1lx4: Solution NMR Structure Of E. coli N-Ada/DNA transcription complex ChemComp-TP0: ChemComp-E5E: ChemComp-41U: ChemComp-PIO: ChemComp-CLR: PDB-1lx7: |
由来 |
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キーワード | TRANSPORT PROTEIN/INHIBITOR / transporter / TRANSPORT PROTEIN-INHIBITOR COMPLEX / transpoter / TRANSPORT PROTEIN / neurotransmitter / transporters / substrate |