Binding of κ-Conotoxin-PVIIA to Open and Closed Shaker K-Channels Are Differentially Affected by the Ionic Strength

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dc.contributor.authorNaranjo, D.
dc.contributor.authorDiaz-Franulic, I.
dc.date.accessioned2021-07-16T14:44:09Z
dc.date.available2021-07-16T14:44:09Z
dc.date.issued2020-10
dc.descriptionIndexación: Scopus.es
dc.description.abstractκ-Conotoxin-PVIIA (κ-PVIIA) is a potassium-channel blocking peptide from the venom of the fish-hunting snail, Conus purpurascens, which is essential for quick prey's excitotoxic immobilization. Binding of one κ-PVIIA to Shaker K-channels occludes the K+-conduction pore without additional conformational effects. Because this 27-residue toxin is +4-charged at neutral pH, we asked if electrostatic interactions play a role in binding. With Voltage-Clamp electrophysiology, we tested how ionic strength (IS) affects κ-PVIIA blockade to Shaker. When IS varied from ~0.06 to ~0.16 M, the dissociation constant for open and closed channels increased by ~5- and ~16-fold, respectively. While the association rates decreased equally, by ~4-fold, in open and closed channels, the dissociation rates increased 4-5-fold in closed channels but was IS-insensitive in open channels. To explain this differential IS-dependency, we propose that the bound κ-PVIIA wobbles, so that in open channels the intracellular environment, via ion-conduction pore, buffers the imposed IS-changes in the toxin-channel interface. A Brønsted-Bjerrum analysis on the rates predicts that if, instead of fish, the snail preyed on organisms with seawater-like lymph ionic composition, a severely harmless toxin, with >100-fold diminished affinity, would result. Thus, considerations of the native ionic environment are essential for conotoxins evaluation as pharmacological leads.es
dc.description.urihttps://www.mdpi.com/1660-3397/18/11/533
dc.identifier.citationMarine drugsOpen AccessVolume 18, Issue 1126 October 2020es
dc.identifier.doi10.3390/md18110533
dc.identifier.issn1660-3397
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/19418
dc.language.isoenes
dc.publisherNLM (Medline)es
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectassociation ratees
dc.subjectBrønsted-Bjerrum equationes
dc.subjectconotoxines
dc.subjectdissociation ratees
dc.subjectKv-channeles
dc.subjectpeptide toxines
dc.subjectpredator-preyes
dc.titleBinding of κ-Conotoxin-PVIIA to Open and Closed Shaker K-Channels Are Differentially Affected by the Ionic Strengthes
dc.typeArtículoes
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