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	Molecular basis of human taurine transporter uptake and inhibition.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 7394, Year 2025
掲載日	2025年8月11日
著者	Bowen Du / Lili Cheng / Jiaying Xie / Ligong Chen / Kaige Yan /
PubMed 要旨	The taurine transporter, TauT, regulates various taurine-mediated physiological and pathological functions by facilitating taurine uptake in a sodium- and chloride-dependent manner. Dysfunction of ...The taurine transporter, TauT, regulates various taurine-mediated physiological and pathological functions by facilitating taurine uptake in a sodium- and chloride-dependent manner. Dysfunction of TauT is associated with male infertility, retinal health and cancers. Despite extensive research efforts, the intricate structure of TauT, the molecular mechanisms underlying taurine transport, and the inhibition mechanisms involved, all remain elusive. Here, we present eleven cryo-electron microscopy (cryo-EM) structures of TauT. The structures TauT bound to substrate (taurine) and substrate analogues (β-alanine, guanidinoacetate, and γ-aminobutyric acid), are captured in distinct conformations. Combining with biochemical analyses, these structures reveal that amino acids Leu134 and Glu406 play a crucial role in substrate specificity within the GABA subfamily. Five distinct inhibitors, namely, piperidine-4-sulfonic acid, imidazole-4-acetatic acid, 5-aminovaleric acid, nipecotic acid and homotaurine, stabilize TauT in an inward-open conformation. Conversely, guanidinoethyl sulphonate stabilizes TauT in the occluded state. These structural insights offer a comprehensive understanding of how these inhibitors counteract taurine transport. Collectively, these findings advance our understanding of the substrate coordination and inhibitor recognition mechanisms of TauT.
リンク	Nat Commun / PubMed:40789850 / PubMed Central
手法	EM (単粒子)
解像度	2.92 - 3.45 Å
構造データ	61943 9k0c EMDB-61943, PDB-9k0c: Cryo-EM structural of human taurine transporter TauT in an apo state 手法: EM (単粒子) / 解像度: 3.06 Å 61948 9k0n EMDB-61948, PDB-9k0n: Cryo-EM structure of human taurine transporter TauT bound with beta-alanine in an occluded state 手法: EM (単粒子) / 解像度: 3.21 Å 61949 9k0o EMDB-61949, PDB-9k0o: Cryo-EM structure of human taurine transporter TauT bound with GAA in an intermediate state during the transport cycle 手法: EM (単粒子) / 解像度: 2.95 Å 61970 9k1b EMDB-61970, PDB-9k1b: Cryo-EM structure of human taurine transporter TauT bound with taurine in an occluded state 手法: EM (単粒子) / 解像度: 3.34 Å 61974 9k1f EMDB-61974, PDB-9k1f: Cryo-EM structure of human taurine transporter TauT bound with GABA in an intermediate conformation in the transport cycle 手法: EM (単粒子) / 解像度: 3.43 Å 61975 9k1h EMDB-61975, PDB-9k1h: Cryo-EM structure of human taurine transporter TauT bound with P4S in an inward open state 手法: EM (単粒子) / 解像度: 3.12 Å 61976 9k1i EMDB-61976, PDB-9k1i: Cryo-EM structure of huamn taurine transporter bound with I4AA in inward-open state 手法: EM (単粒子) / 解像度: 2.92 Å 61981 9k1v EMDB-61981, PDB-9k1v: Cryo-EM structure of human taurine transporter bound with 5AVA in an inward-open state 手法: EM (単粒子) / 解像度: 2.94 Å 61983 9k1x EMDB-61983, PDB-9k1x: Cryo-EM structure of human taurine transporter TauT bound with GES in an occluded state 手法: EM (単粒子) / 解像度: 3.06 Å 61985 9k1z EMDB-61985, PDB-9k1z: Cryo-EM structure of human taurine transporter bound with nipecotic acid in an inward open state 手法: EM (単粒子) / 解像度: 3.27 Å 61987 9k21 EMDB-61987, PDB-9k21: Cryo-EM structure of human taurine transporter TauT bound with homotaurine in an inward-open state 手法: EM (単粒子) / 解像度: 3.45 Å
化合物	ChemComp-CL: Unknown entry / クロリド ChemComp-BAL: BETA-ALANINE / β-アラニン ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-NMG: GUANIDINO ACETATE / グアニジノ酢酸 ChemComp-TAU: 2-AMINOETHANESULFONIC ACID / タウリン ChemComp-ABU: GAMMA-AMINO-BUTANOIC ACID / GABA / 神経伝達物質, 阻害剤YM PDB-1ebd: DIHYDROLIPOAMIDE DEHYDROGENASE COMPLEXED WITH THE BINDING DOMAIN OF THE DIHYDROLIPOAMIDE ACETYLASE ChemComp-IZC: 2H-IMIDAZOL-4-YLACETIC ACID / 神経伝達物質YM ChemComp-HOH: WATER ChemComp-KFB: 5-Aminovaleric Acid / 5-アミノ吉草酸 ChemComp-3S5: Taurocyamine / タウロシアミン ChemComp-ID7: (3R)-piperidine-3-carboxylic acid / (R)-ニペコチン酸 ChemComp-A20: 3-aminopropane-1-sulfonic acid / ホモタウリン
由来	homo sapiens (ヒト)
キーワード	STRUCTURAL PROTEIN/IMMUNE SYSTEM / CL / TRANSPORT PROTEIN / STRUCTURAL PROTEIN-IMMUNE SYSTEM complex / substrate / structural / protein / substrate protein transporter / Inhibitor