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

Abstract

Highlights: • We have made a reasonable model of rat ASIC3 using published structure of chicken ASIC1. • We have docked sea anemone toxin APETx2 on the model. • We have identified two putative sites for toxin binding. • We have argued for plausibility one site over the other. • We have identified the residues that are likely to be critical for APETx2–ASIC3 interaction. - 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, themore » 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.« less

Authors:
;
Publication Date:
OSTI Identifier:
22416633
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL MODELS; CATIONS; CHICKENS; COMPUTERIZED SIMULATION; INACTIVATION; MODULATION; NERVE CELLS; NERVOUS SYSTEM; PROTEINS; RATS; RESIDUES; STIMULI; STRUCTURE FUNCTIONS; TOXINS

Citation Formats

Rahman, Taufiq, and Smith, Ewan St. John. In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.05.130.
Rahman, Taufiq, & Smith, Ewan St. John. In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3. United States. https://doi.org/10.1016/J.BBRC.2014.05.130
Rahman, Taufiq, and Smith, Ewan St. John. 2014. "In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3". United States. https://doi.org/10.1016/J.BBRC.2014.05.130.
@article{osti_22416633,
title = {In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3},
author = {Rahman, Taufiq and Smith, Ewan St. John},
abstractNote = {Highlights: • We have made a reasonable model of rat ASIC3 using published structure of chicken ASIC1. • We have docked sea anemone toxin APETx2 on the model. • We have identified two putative sites for toxin binding. • We have argued for plausibility one site over the other. • We have identified the residues that are likely to be critical for APETx2–ASIC3 interaction. - 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.},
doi = {10.1016/J.BBRC.2014.05.130},
url = {https://www.osti.gov/biblio/22416633}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 450,
place = {United States},
year = {Fri Jul 18 00:00:00 EDT 2014},
month = {Fri Jul 18 00:00:00 EDT 2014}
}