Identifying human diamine sensors for death related putrescine and cadaverine molecules

PLoS Comput Biol. 2018 Jan 11;14(1):e1005945. doi: 10.1371/journal.pcbi.1005945. eCollection 2018 Jan.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / chemistry
  • Behavior, Animal
  • Cadaverine / chemistry*
  • Cell Cycle Proteins / chemistry
  • Computational Biology
  • Computer Simulation
  • Diamines / chemistry*
  • Humans
  • Ligands
  • Molecular Docking Simulation
  • Nuclear Proteins / chemistry
  • Olfactory Mucosa / physiology
  • Phylogeny
  • Polyamines / chemistry
  • Protein Binding
  • Putrescine / chemistry*
  • Receptors, G-Protein-Coupled / chemistry
  • Smell*
  • Zebrafish

Substances

  • Cell Cycle Proteins
  • Diamines
  • Ligands
  • Nuclear Proteins
  • Polyamines
  • Receptors, G-Protein-Coupled
  • TAAR8 protein, human
  • trace amine receptor 4, human
  • Aspartic Acid
  • Cadaverine
  • Putrescine

Grants and funding

This study was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) (www.mineco.gob.es/) research grant to LP, SAF2016-77830-R and AG ‘Juan de la Cierva’ FJCI-2014-23113 postdoctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.