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


Type
Article
Change log
Authors
Rahman, T 
Smith, ESJ 
Abstract

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.

Description
Keywords
APETx2, ASIC3, Homology modelling, Protein–protein docking, Acid Sensing Ion Channels, Animals, Binding Sites, Chickens, Cnidarian Venoms, Computer Simulation, Lipid Bilayers, Models, Chemical, Models, Molecular, Protein Binding, Protein Conformation, Rats
Journal Title
Biochem Biophys Res Commun
Conference Name
Journal ISSN
0006-291X
1090-2104
Volume Title
450
Publisher
Elsevier
Sponsorship
T.R. is a recipient of a fellowship and additional support funding (RG120370) from the Royal Society.