21AG
LY334370-bound serotonin 1F (5-HT1F) receptor-miniGoA protein complex
This is a non-PDB format compatible entry.
Summary for 21AG
| Entry DOI | 10.2210/pdb21ag/pdb |
| EMDB information | 67446 |
| Descriptor | Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total) |
| Functional Keywords | membrane protein/immune system, membrane protein-immune system complex |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 143496.65 |
| Authors | |
| Primary citation | Wang, Y.,Wang, C.,Cao, C. Structural basis of LY334370 recognition and selectivity at the 5-HT 1F receptor. Biochem.Biophys.Res.Commun., 804:153313-153313, 2026 Cited by PubMed Abstract: The 5-HT receptor is a serotonin receptor subtype highly expressed in trigeminal sensory neurons, where it modulates neuropeptide release and nociceptive signaling without inducing vasoconstriction. This makes it an important therapeutic target for migraine. LY334370 was developed as a first-generation selective 5-HTR agonist and demonstrated efficacy in clinical studies. However, the molecular mechanism underlying 5-HTR activation by LY334370 remains poorly understood. Here, we determined a 3.13 Å cryo-EM structure of the LY334370-bound 5-HTR-miniGα complex. Combined with functional analyses, this structure delineates the molecular determinants underlying LY334370 recognition. Comparison with BRL54443 indicates that LY334370 selectivity for 5-HTR is driven by its optimal accommodation within the receptor-specific extended binding pocket. Furthermore, comparative analysis with the lasmiditan-bound 5-HTR-Gα complex reveals distinct agonist binding modes and provides mechanistic insight into Gα subtype-specific coupling. Collectively, these findings elucidate the structural basis of 5-HTR activation, ligand selectivity, and G protein coupling, providing a structural framework for the rational design of safer and more effective anti-migraine drugs. PubMed: 41619505DOI: 10.1016/j.bbrc.2026.153313 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.13 Å) |
Structure validation
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