Identifying human diamine sensors for death related putrescine and cadaverine molecules
Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by decarboxylation of amino acids during decomposition. These volatile p...
| Autores: | , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:187855 |
| Acceso en línea: | https://ddd.uab.cat/record/187855 https://dx.doi.org/urn:doi:10.1371/journal.pcbi.1005945 |
| Access Level: | acceso abierto |
| Palabra clave: | Animals Aspartic Acid Behavior, Animal Cadaverine Cell cycle proteins Computer simulation Putrescine Smell |
| Sumario: | Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by decarboxylation of amino acids during decomposition. These volatile polyamines act as 'necromones', triggering avoidance or attractive responses, which are fundamental for the survival of a wide range of species. The few studies that have attempted to identify the cognate receptors for these molecules have suggested the involvement of the seven-helix trace amine-associated receptors (TAARs), localized in the olfactory epithelium. However, very little is known about the precise chemosensory receptors that sense these compounds in the majority of organisms and the molecular basis of their interactions. In this work, we have used computational strategies to characterize the binding between PUT and CAD with the TAAR6 and TAAR8 human receptors. Sequence analysis, homology modeling, docking and molecular dynamics studies suggest a tandem of negatively charged aspartates in the binding pocket of these receptors which are likely to be involved in the recognition of these small biogenic diamines. The distinctive dead smell comes largely from molecules like cadaverine and putrescine that are produced during decomposition of organic tissues. These volatile compounds act as powerful chemical signals important for the survival of a wide range of species. Previous studies have identified the trace amine-associated receptor 13c (or TAAR13c) in zebrafish as the cognate receptor of cadaverine in bony fishes. In this work, we employed computational strategies to disclose the human TAAR6 and TAAR8 receptors as sensors of the putrescine and cadaverine molecules. Our results indicate that several negatively charged residues in the ligand binding pocket of these receptors constitute the molecular basis for recognition of these necromones in humans. |
|---|