Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
APETx-Like Peptides from the Sea Anemone Heteractis crispa, Diverse in Their Effect on ASIC1a and ASIC3 Ion Channels.
Kalina RS
,
Koshelev SG
,
Zelepuga EA
,
Kim NY
,
Kozlov SA
,
Kozlovskaya EP
,
Monastyrnaya MM
,
Gladkikh IN
.
???displayArticle.abstract???
Currently, five peptide modulators of acid-sensing ion channels (ASICs) attributed to structural class 1b of sea anemone toxins have been described. The APETx2 toxin is the first and most potent ASIC3 inhibitor, so its homologs from sea anemones are known as the APETx-like peptides. We have discovered that two APETx-like peptides from the sea anemone Heteractis crispa, Hcr 1b-3 and Hcr 1b-4, demonstrate different effects on rASIC1a and rASIC3 currents. While Hcr 1b-3 inhibits both investigated ASIC subtypes with IC50 4.95 ± 0.19 μM for rASIC1a and 17 ± 5.8 μM for rASIC3, Hcr 1b-4 has been found to be the first potentiator of ASIC3, simultaneously inhibiting rASIC1a at similar concentrations: EC50 1.53 ± 0.07 μM and IC50 1.25 ± 0.04 μM. The closest homologs, APETx2, Hcr 1b-1, and Hcr 1b-2, previously demonstrated the ability to inhibit hASIC3 with IC50 63 nM, 5.5, and 15.9 μM, respectively, while Hcr 1b-2 also inhibited rASIC1a with IC50 4.8 ± 0.3 μM. Computer modeling allowed us to describe the peculiarities of Hcr 1b-2 and Hcr 1b-4 interfaces with the rASIC1a channel and the stabilization of the expanded acidic pocket resulting from peptides binding which traps the rASIC1a channel in the closed state.
Andreev,
Analgesic Activity of Acid-Sensing Ion Channel 3 (ASIС3) Inhibitors: Sea Anemones Peptides Ugr9-1 and APETx2 versus Low Molecular Weight Compounds.
2018, Pubmed,
Xenbase
Andreev,
Analgesic Activity of Acid-Sensing Ion Channel 3 (ASIС3) Inhibitors: Sea Anemones Peptides Ugr9-1 and APETx2 versus Low Molecular Weight Compounds.
2018,
Pubmed
,
Xenbase
Baconguis,
X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.
2014,
Pubmed
Baconguis,
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
2012,
Pubmed
Bohlen,
A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain.
2011,
Pubmed
,
Xenbase
Camacho,
BLAST+: architecture and applications.
2009,
Pubmed
Chagot,
Solution structure of APETx1 from the sea anemone Anthopleura elegantissima: a new fold for an HERG toxin.
2005,
Pubmed
Chagot,
Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels.
2005,
Pubmed
Chassagnon,
Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a.
2017,
Pubmed
Chu,
Physiological and pathological functions of acid-sensing ion channels in the central nervous system.
2012,
Pubmed
Cristofori-Armstrong,
Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms.
2017,
Pubmed
Dawson,
Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1.
2012,
Pubmed
Dibas,
Basics on the use of acid-sensing ion channels' inhibitors as therapeutics.
2019,
Pubmed
Diochot,
A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.
2004,
Pubmed
,
Xenbase
Diochot,
APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels.
2003,
Pubmed
Diochot,
Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4.
1998,
Pubmed
,
Xenbase
Driscoll,
Determination of the three-dimensional solution structure of the antihypertensive and antiviral protein BDS-I from the sea anemone Anemonia sulcata: a study using nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing.
1989,
Pubmed
Dubinnyi,
Lignan from thyme possesses inhibitory effect on ASIC3 channel current.
2012,
Pubmed
,
Xenbase
Er,
Discovery and molecular interaction studies of a highly stable, tarantula peptide modulator of acid-sensing ion channel 1.
2017,
Pubmed
,
Xenbase
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Gründer,
Biophysical properties of acid-sensing ion channels (ASICs).
2015,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Jensen,
Understanding the molecular basis of toxin promiscuity: the analgesic sea anemone peptide APETx2 interacts with acid-sensing ion channel 3 and hERG channels via overlapping pharmacophores.
2014,
Pubmed
Kalina,
New APETx-like peptides from sea anemone Heteractis crispa modulate ASIC1a channels.
2018,
Pubmed
,
Xenbase
Kim,
Defensin-neurotoxin dyad in a basally branching metazoan sea anemone.
2017,
Pubmed
Koradi,
MOLMOL: a program for display and analysis of macromolecular structures.
1996,
Pubmed
Kozakov,
How good is automated protein docking?
2013,
Pubmed
Kozlov,
Convenient nomenclature of cysteine-rich polypeptide toxins from sea anemones.
2012,
Pubmed
Kozlov,
[Polypeptide toxin from sea anemone inhibiting proton-sensitive channel ASIC3].
2012,
Pubmed
,
Xenbase
Laskowski,
AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR.
1996,
Pubmed
Lee,
Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain.
2018,
Pubmed
,
Xenbase
Leffler,
Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models.
2017,
Pubmed
Lin,
Genetic exploration of the role of acid-sensing ion channels.
2015,
Pubmed
Liu,
Modulation of neuronal sodium channels by the sea anemone peptide BDS-I.
2012,
Pubmed
Lu,
Vector NTI, a balanced all-in-one sequence analysis suite.
2004,
Pubmed
Macrander,
Multi-copy venom genes hidden in de novo transcriptome assemblies, a cautionary tale with the snakelocks sea anemone Anemonia sulcata (Pennant, 1977).
2015,
Pubmed
Mikov,
[Structural Features of Cysteine-Stabilized Polypeptides from Sea Anemones Venoms].
2015,
Pubmed
Moreels,
APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel KV10.1.
2017,
Pubmed
,
Xenbase
Mourier,
Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition.
2016,
Pubmed
,
Xenbase
Newport,
The MemProtMD database: a resource for membrane-embedded protein structures and their lipid interactions.
2019,
Pubmed
Osmakov,
Acid-sensing ion channels and their modulators.
2014,
Pubmed
Osmakov,
Sea anemone peptide with uncommon β-hairpin structure inhibits acid-sensing ion channel 3 (ASIC3) and reveals analgesic activity.
2013,
Pubmed
,
Xenbase
Peigneur,
A natural point mutation changes both target selectivity and mechanism of action of sea anemone toxins.
2012,
Pubmed
,
Xenbase
Pettersen,
UCSF Chimera--a visualization system for exploratory research and analysis.
2004,
Pubmed
Reimers,
Identification of a cono-RFamide from the venom of Conus textile that targets ASIC3 and enhances muscle pain.
2017,
Pubmed
,
Xenbase
Rodríguez,
Peptide fingerprinting of the neurotoxic fractions isolated from the secretions of sea anemones Stichodactyla helianthus and Bunodosoma granulifera. New members of the APETx-like family identified by a 454 pyrosequencing approach.
2012,
Pubmed
Saez,
Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a.
2015,
Pubmed
,
Xenbase
Sali,
Comparative protein modelling by satisfaction of spatial restraints.
1993,
Pubmed
Soto,
Protons as Messengers of Intercellular Communication in the Nervous System.
2018,
Pubmed
Sreerama,
Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set.
2000,
Pubmed
Sun,
Cryo-EM structure of the ASIC1a-mambalgin-1 complex reveals that the peptide toxin mambalgin-1 inhibits acid-sensing ion channels through an unusual allosteric effect.
2018,
Pubmed
Uchitel,
Synaptic signals mediated by protons and acid-sensing ion channels.
2019,
Pubmed
Vullo,
A molecular view of the function and pharmacology of acid-sensing ion channels.
2020,
Pubmed
Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed
Wemmie,
Acid-sensing ion channels in pain and disease.
2013,
Pubmed
Wu,
ASIC subunit ratio and differential surface trafficking in the brain.
2016,
Pubmed
Yeung,
Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies.
2005,
Pubmed
Yoder,
Gating mechanisms of acid-sensing ion channels.
2018,
Pubmed
Yoder,
Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography.
2018,
Pubmed
Yu,
Molecular dynamics simulations investigate the mechanism of Psalmotoxin 1 regulating gating process of an acid-sensing ion channel 1a at pH 5.5.
2018,
Pubmed
Zaharenko,
Proteomics of the neurotoxic fraction from the sea anemone Bunodosoma cangicum venom: Novel peptides belonging to new classes of toxins.
2008,
Pubmed
Zhou,
Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases.
2016,
Pubmed
