EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Illumination of serotonin transporter mechanism and role of the allosteric site.
ジャーナル・号・ページ	Sci Adv, Vol. 7, Issue 49, Page eabl3857, Year 2021
掲載日	2021年12月3日
著者	Dongxue Yang / Eric Gouaux /
PubMed 要旨	The serotonin transporter (SERT) terminates serotonin signaling by using sodium and chloride gradients to drive reuptake of serotonin into presynaptic neurons and is the target of widely used ...The serotonin transporter (SERT) terminates serotonin signaling by using sodium and chloride gradients to drive reuptake of serotonin into presynaptic neurons and is the target of widely used medications to treat neuropsychiatric disorders. Despite decades of study, the molecular mechanism of serotonin transport, the coupling to ion gradients, and the role of the allosteric site have remained elusive. Here, we present cryo–electron microscopy structures of SERT in serotonin-bound and serotonin-free states, in the presence of sodium or potassium, resolving all fundamental states of the transport cycle. From the SERT-serotonin complex, we localize the substrate-bound allosteric site, formed by an aromatic pocket positioned in the scaffold domain in the extracellular vestibule, connected to the central site via a short tunnel. Together with elucidation of multiple apo state conformations, we provide previously unseen structural understanding of allosteric modulation, demonstrating how SERT binds serotonin from synaptic volumes and promotes unbinding into the presynaptic neurons.
リンク	Sci Adv / PubMed:34851672 / PubMed Central
手法	EM (単粒子)
解像度	3.3 - 4.1 Å
構造データ	23361 7li6 EMDB-23361, PDB-7li6: apo SERT reconstituted in lipid nanodisc in KCl 手法: EM (単粒子) / 解像度: 3.5 Å 23362 7li7 EMDB-23362, PDB-7li7: apo serotonin transporter reconstituted in lipid nanodisc in presence of NaCl in occluded conformation 手法: EM (単粒子) / 解像度: 4.1 Å 23363 7li8 EMDB-23363, PDB-7li8: apo serotonin transporter reconstituted in lipid nanodisc in presence of NaCl in inward open conformation 手法: EM (単粒子) / 解像度: 3.9 Å 23364 7li9 EMDB-23364, PDB-7li9: 5-HT bound serotonin transporter reconstituted in lipid nanodisc in KCl 手法: EM (単粒子) / 解像度: 3.9 Å 23365 7lia EMDB-23365, PDB-7lia: 5-HT bound serotonin transporter reconstituted in lipid nanodisc in presence of NaCl in outward facing conformation 手法: EM (単粒子) / 解像度: 3.3 Å 23830 7mgw EMDB-23830, PDB-7mgw: 5-HT bound serotonin transporter reconstituted in lipid nanodisc in NaCl in occluded conformation 手法: EM (単粒子) / 解像度: 3.5 Å
化合物	ChemComp-CL: Unknown entry / クロリド ChemComp-R16: HEXADECANE / ヘキサデカン ChemComp-HP6: HEPTANE / ヘプタン-1,1,1-トリイルラジカル ChemComp-D10: DECANE / デカン ChemComp-D12: DODECANE / ドデカン ChemComp-LNK: PENTANE / ペンタン ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-SRO: SEROTONIN / セロトニン / 神経伝達物質YM ChemComp-NA*: Unknown entry / ナトリウムカチオン
由来	homo sapiens (ヒト) Mouse (ネズミ) mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / serotonin / human serotonin transporter / transport / Fab / occluded / serotonin transporter / inward / KCl / outward open