Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Pathway-selective 5-HTR agonist as a rapid antidepressant strategy.
Journal, issue, pages	Cell, Vol. 188, Issue 25, Page 7222-7237.e24, Year 2025
Publish date	Dec 11, 2025
Authors	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 Abstract	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.
External links	Cell / PubMed:41232528
Methods	EM (single particle)
Resolution	2.47 - 2.86 Å
Structure data	65104 9vj5 EMDB-65104, PDB-9vj5: Cryo-EM structure of 5-HT1AR-GoA in complex with gepirone Method: EM (single particle) / Resolution: 2.69 Å 65105 9vj6 EMDB-65105, PDB-9vj6: Cryo-EM structure of 5-HT1AR-Gi3 in complex with F-15599 Method: EM (single particle) / Resolution: 2.62 Å 65110 9vje EMDB-65110, PDB-9vje: Cryo-EM structure of 5-HT1AR-GoA in complex with buspirone Method: EM (single particle) / Resolution: 2.47 Å 65111 9vjf EMDB-65111, PDB-9vjf: Cryo-EM structure of 5-HT1AR-Gi3 in complex with buspirone Method: EM (single particle) / Resolution: 2.7 Å 65112 9vjg EMDB-65112, PDB-9vjg: Cryo-EM structure of 5-HT1AR-Gz in complex with (R)-8-OH-DPAT Method: EM (single particle) / Resolution: 2.67 Å 65196 9vmy EMDB-65196, PDB-9vmy: Cryo-EM structure of 5-HT1AR-GoA in complex with TMU4142 Method: EM (single particle) / Resolution: 2.86 Å 65210 9vnf EMDB-65210, PDB-9vnf: Cryo-EM structure of 5-HT1AR-GoA in complex with (S)-pindolol Method: EM (single particle) / Resolution: 2.74 Å
Chemicals	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 ChemComp, No image 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
Source	homo sapiens (human) mus musculus (house mouse) escherichia coli (E. coli)
Keywords	MEMBRANE PROTEIN / signal transduction