In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3.

Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed throughout the nervous system and have been implicated in mediating sensory perception of noxious stimuli. Amongst the six ASIC isoforms, ASIC1a, 1b, 2a and 3 form proton-gated homomers, which differ in their activation and inactivation kinetics, expression profiles and pharmacological modulation; protons do not gate ASIC2b and ASIC4. As with many other ion channels, structure-function studies of ASICs have been greatly aided by the discovery of some toxins that act in isoform-specific ways. ASIC3 is predominantly expressed by sensory neurons of the peripheral nervous system where it acts to detect acid as a noxious stimulus and thus plays an important role in nociception. ASIC3 is the only ASIC subunit that is inhibited by the sea anemone (Anthopleura elegantissima)-derived toxin APETx2. However, the molecular mechanism by which APETx2 interacts with ASIC3 remains largely unknown. In this study, we made a homology model of ASIC3 and used extensive protein-protein docking to predict for the first time, the probable sites of APETx2 interaction on ASIC3. Additionally, using computational alanine scanning, we also suggest the 'hot-spots' that are likely to be critical for ASIC3-APETx2 interaction.

Rahman T ，Smith ES 《-》

Peptides inhibitors of acid-sensing ion channels.

Diochot S ，Salinas M ，Baron A ，Escoubas P ，Lazdunski M ... -  《TOXICON》

A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.

Diochot S ，Baron A ，Rash LD ，Deval E ，Escoubas P ，Scarzello S ，Salinas M ，Lazdunski M ... -  《-》

Functional expression in Escherichia coli of the disulfide-rich sea anemone peptide APETx2, a potent blocker of acid-sensing ion channel 3.

Anangi R ，Rash LD ，Mobli M ，King GF ... -  《Marine Drugs》

Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels.

Chagot B ，Escoubas P ，Diochot S ，Bernard C ，Lazdunski M ，Darbon H ... -  《-》