RESUMO
Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors1,2 (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion3-5. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9-Gs or mTAAR9-Golf trimers in complex with ß-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D3.32W6.48Y7.43 motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to Gs and Golf by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golf coupling of an amine olfactory receptor.
Assuntos
Aminas Biogênicas , Odorantes , Percepção Olfatória , Poliaminas , Receptores Odorantes , Animais , Camundongos , Aminas Biogênicas/análise , Aminas Biogênicas/química , Aminas Biogênicas/metabolismo , Microscopia Crioeletrônica , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/ultraestrutura , Odorantes/análise , Percepção Olfatória/fisiologia , Poliaminas/análise , Poliaminas/química , Poliaminas/metabolismo , Receptores de Amina Biogênica/química , Receptores de Amina Biogênica/genética , Receptores de Amina Biogênica/metabolismo , Receptores de Amina Biogênica/ultraestrutura , Receptores Odorantes/química , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/ultraestrutura , Olfato/fisiologia , Espermidina/análise , Espermidina/química , Espermidina/metabolismoRESUMO
Mediastinal pleura was studied in pregnancy second part abortive human fetuses using histological and histochemical technique. It was found to have a well-developed monoaminergic apparatus that includes adrenergic axons and mast cells. Electron microscope study confirmed monoaminergic and single peptidergic vesicles presence in axons. Luminescent method revealed that mast cells of nerve plexuses and blood vessels contain catecholamines and indolalkylamines. Monoaminergic axons and mast cells were shown to constitute a functionally integrative apparatus that regulates local hemodynamics and trophics.
