The N-terminal Ankyrin Repeat Domain Is Not Required for Electrophile and Heat Activation of the Purified Mosquito TRPA1 Receptor

J Biol Chem. 2016 Dec 23;291(52):26899-26912. doi: 10.1074/jbc.M116.743443. Epub 2016 Nov 14.

Abstract

Temperature sensors are crucial for animals to optimize living conditions. The temperature response of the ion channel transient receptor potential A1 (TRPA1) is intriguing; some orthologs have been reported to be activated by cold and others by heat, but the molecular mechanisms responsible for its activation remain elusive. Single-channel electrophysiological recordings of heterologously expressed and purified Anopheles gambiae TRPA1 (AgTRPA1), with and without the N-terminal ankyrin repeat domain, demonstrate that both proteins are functional because they responded to the electrophilic compounds allyl isothiocyanate and cinnamaldehyde as well as heat. The proteins' similar intrinsic fluorescence properties and corresponding quenching when activated by allyl isothiocyanate or heat suggest lipid bilayer-independent conformational changes outside the N-terminal domain. The results show that AgTRPA1 is an inherent thermo- and chemoreceptor, and analogous to what has been reported for the human TRPA1 ortholog, the N-terminal domain may tune the response but is not required for the activation by these stimuli.

Keywords: fluorescence; heat sensing; pain; patch clamp; repellents; thermosensor; transient receptor potential channels (TRP channels); tryptophan.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ankyrin Repeat*
  • Binding Sites
  • Cold Temperature
  • Crystallography, X-Ray
  • Culicidae / metabolism*
  • Hot Temperature
  • Humans
  • Ion Channel Gating / physiology*
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Transient Receptor Potential Channels / isolation & purification
  • Transient Receptor Potential Channels / metabolism*

Substances

  • Transient Receptor Potential Channels

Associated data

  • PDB/3J9P