Next Article in Journal
Multiwalled Carbon Nanotube for One-Step Cleanup of 21 Mycotoxins in Corn and Wheat Prior to Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry Analysis
Previous Article in Journal
Protective Effect of N-Acetylcysteine against Oxidative Stress Induced by Zearalenone via Mitochondrial Apoptosis Pathway in SIEC02 Cells
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Toxins 2018, 10(10), 408; https://doi.org/10.3390/toxins10100408

Purification and Characterization of JZTx-14, a Potent Antagonist of Mammalian and Prokaryotic Voltage-Gated Sodium Channels

The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 3 September 2018 / Revised: 4 October 2018 / Accepted: 6 October 2018 / Published: 10 October 2018
(This article belongs to the Special Issue Toxins-Membrane Interactions)
Full-Text   |   PDF [5286 KB, uploaded 14 October 2018]   |  

Abstract

Exploring the interaction of ligands with voltage-gated sodium channels (NaVs) has advanced our understanding of their pharmacology. Herein, we report the purification and characterization of a novel non-selective mammalian and bacterial NaVs toxin, JZTx-14, from the venom of the spider Chilobrachys jingzhao. This toxin potently inhibited the peak currents of mammalian NaV1.2–1.8 channels and the bacterial NaChBac channel with low IC50 values (<1 µM), and it mainly inhibited the fast inactivation of the NaV1.9 channel. Analysis of NaV1.5/NaV1.9 chimeric channel showed that the NaV1.5 domain II S3–4 loop is involved in toxin association. Kinetics data obtained from studying toxin–NaV1.2 channel interaction showed that JZTx-14 was a gating modifier that possibly trapped the channel in resting state; however, it differed from site 4 toxin HNTx-III by irreversibly blocking NaV currents and showing state-independent binding with the channel. JZTx-14 might stably bind to a conserved toxin pocket deep within the NaV1.2–1.8 domain II voltage sensor regardless of channel conformation change, and its effect on NaVs requires the toxin to trap the S3–4 loop in its resting state. For the NaChBac channel, JZTx-14 positively shifted its conductance-voltage (G–V) and steady-state inactivation relationships. An alanine scan analysis of the NaChBac S3–4 loop revealed that the 108th phenylalanine (F108) was the key residue determining the JZTx-14–NaChBac interaction. In summary, this study provided JZTx-14 with potent but promiscuous inhibitory activity on both the ancestor bacterial NaVs and the highly evolved descendant mammalian NaVs, and it is a useful probe to understand the pharmacology of NaVs. View Full-Text
Keywords: NaChBac; mammalian NaVs; peptide toxin; pharmacology NaChBac; mammalian NaVs; peptide toxin; pharmacology
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Zhang, J.; Tang, D.; Liu, S.; Hu, H.; Liang, S.; Tang, C.; Liu, Z. Purification and Characterization of JZTx-14, a Potent Antagonist of Mammalian and Prokaryotic Voltage-Gated Sodium Channels. Toxins 2018, 10, 408.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top