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	Pathway-selective 5-HTR agonist as a rapid antidepressant strategy.
ジャーナル・号・ページ	Cell, Vol. 188, Issue 25, Page 7222-7237.e24, Year 2025
掲載日	2025年12月11日
著者	Chunyu Wang / Nan Zhang / Yujie Shao / Tao Li / Mengna Zhang / Meng Gao / Yaqi Liang / Yumeng Wang / Tian Xue / Yiming Shi / He Chen / Can Cao /
PubMed 要旨	Presynaptic 5-HTR autoreceptors predominantly signal through G protein, mediating feedback inhibition that hampers the therapeutic efficacy of conventional antidepressants. By contrast, postsynaptic ...Presynaptic 5-HTR autoreceptors predominantly signal through G protein, mediating feedback inhibition that hampers the therapeutic efficacy of conventional antidepressants. By contrast, postsynaptic heteroreceptors mainly couple to G, which promotes antidepressant responses. However, selectively activating heteroreceptors while bypassing the negative feedback induced by autoreceptors remains a significant challenge. Here, we characterized the G subtype signaling profiles of 5-HTR and determined its structures in complex with six agonists and three distinct G family proteins: G, G, and G. Combined with functional analysis, we elucidated the mechanisms underlying diverse agonist recognition modes and G subtype signaling selectivity of 5-HTR. Furthermore, we designed a pathway-selective agonist, TMU4142, which exhibits high G activity while minimizing G activation. Remarkably, TMU4142 demonstrated rapid antidepressant-like effects in a mouse model of depression. Collectively, these findings suggest that distinguishing heteroreceptors from autoreceptors based on their distinct downstream G signaling pathways could be a promising strategy to develop fast-acting antidepressants.
リンク	Cell / PubMed:41232528
手法	EM (単粒子)
解像度	2.47 - 2.86 Å
構造データ	65104 9vj5 EMDB-65104, PDB-9vj5: Cryo-EM structure of 5-HT1AR-GoA in complex with gepirone 手法: EM (単粒子) / 解像度: 2.69 Å 65105 9vj6 EMDB-65105, PDB-9vj6: Cryo-EM structure of 5-HT1AR-Gi3 in complex with F-15599 手法: EM (単粒子) / 解像度: 2.62 Å 65110 9vje EMDB-65110, PDB-9vje: Cryo-EM structure of 5-HT1AR-GoA in complex with buspirone 手法: EM (単粒子) / 解像度: 2.47 Å 65111 9vjf EMDB-65111, PDB-9vjf: Cryo-EM structure of 5-HT1AR-Gi3 in complex with buspirone 手法: EM (単粒子) / 解像度: 2.7 Å 65112 9vjg EMDB-65112, PDB-9vjg: Cryo-EM structure of 5-HT1AR-Gz in complex with (R)-8-OH-DPAT 手法: EM (単粒子) / 解像度: 2.67 Å 65196 9vmy EMDB-65196, PDB-9vmy: Cryo-EM structure of 5-HT1AR-GoA in complex with TMU4142 手法: EM (単粒子) / 解像度: 2.86 Å 65210 9vnf EMDB-65210, PDB-9vnf: Cryo-EM structure of 5-HT1AR-GoA in complex with (S)-pindolol 手法: EM (単粒子) / 解像度: 2.74 Å
化合物	PDB-1esa: DIRECT STRUCTURE OBSERVATION OF AN ACYL-ENZYME INTERMEDIATE IN THE HYDROLYSIS OF AN ESTER SUBSTRATE BY ELASTASE ChemComp-CLR: CHOLESTEROL ChemComp-T7M: (2R)-1-(heptadecanoyloxy)-3-{[(R)-hydroxy{[(1R,2R,3R,4R,5S,6R)-2,3,5,6-tetrahydroxy-4-(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate PDB-1esc: THE MOLECULAR MECHANISM OF ENANTIORECOGNITION BY ESTERASES 化合物画像なし ChemComp-YLX: Unknown entry PDB-1ese: THE MOLECULAR MECHANISM OF ENANTIORECOGNITION BY ESTERASES PDB-1es2: S96A mutant of streptomyces K15 DD-transpeptidase PDB-1es4: C98N mutant of streptomyces K15 DD-transpeptidase
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ) escherichia coli (大腸菌)
キーワード	MEMBRANE PROTEIN / signal transduction