8ZSV
Cryo-EM structure of the RO5263397-bound mTAAR1-Gs complex
This is a non-PDB format compatible entry.
Summary for 8ZSV
| Entry DOI | 10.2210/pdb8zsv/pdb |
| EMDB information | 60427 |
| Descriptor | Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total) |
| Functional Keywords | gpcr, taar1, cryo-em, membrane protein/immune system, membrane protein-immune system complex |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 144773.91 |
| Authors | Jiang, K.X.,Zheng, Y.,Xu, F. (deposition date: 2024-06-05, release date: 2024-07-24, Last modification date: 2024-10-23) |
| Primary citation | Jiang, K.,Zheng, Y.,Zeng, L.,Wang, L.,Li, F.,Pu, J.,Lu, Y.,Zhao, S.,Xu, F. The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules. Cell Rep, 43:114505-114505, 2024 Cited by PubMed Abstract: Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs. PubMed: 39002128DOI: 10.1016/j.celrep.2024.114505 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.96 Å) |
Structure validation
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