Jingzhaotoxin-III selectively inhibits the activation of the voltage-dependent Nav1.5 channels (IC50 = 350 nM) in heart or cancer cells, but displays no effect on other isoforms,like NaV1.2, NaV1.4, NaV1.6 and NaV1.7. It also inhibits Kv2.1 channel (IC50 = 700 nM).
CAT No: R0983
CAS No:925463-91-8
Synonyms/Alias:jingzhaotoxin-III;925463-91-8;Jingzhaotoxin III;AMB46391;AKOS024458414;DA-54534;PD079774;
Jingzhaotoxin III is a peptide neurotoxin originally isolated from the venom of the Chinese tarantula Chilobrachys jingzhao. As a member of the spider toxin family, it is characterized by a compact, cysteine-rich structure that confers notable stability and specificity for certain voltage-gated ion channels. Its unique molecular architecture and highly selective activity have made it a valuable tool in neurophysiological research, particularly in the study of ion channel function and synaptic transmission. Jingzhaotoxin III's ability to modulate the activity of neuronal membranes has positioned it as an important reagent for dissecting the molecular mechanisms underlying excitability and signal propagation in excitable tissues.
Ion channel research: Jingzhaotoxin III is widely utilized for the functional characterization of voltage-gated sodium and potassium channels in neuronal and muscle tissues. By selectively interacting with specific channel subtypes, it enables researchers to delineate the roles of individual channels in action potential initiation and propagation. The peptide's high affinity and subtype selectivity allow for precise mapping of channel pharmacology, facilitating the identification of channelopathies and the development of new strategies for modulating electrical signaling in excitable cells.
Neuropharmacological studies: The toxin's potent modulation of ion channel gating kinetics makes it an indispensable tool in neuropharmacology. By applying Jingzhaotoxin III to isolated neurons or heterologously expressed channels, scientists can investigate the consequences of altered channel function on synaptic transmission and neuronal excitability. Such studies provide critical insights into the pathophysiology of neurological disorders associated with dysfunctional ion channel activity, as well as the discovery of potential molecular targets for pharmacological intervention.
Structure-function analysis: The defined sequence and disulfide-rich tertiary structure of Jingzhaotoxin III render it an exemplary model for structure-activity relationship investigations. Researchers employ site-directed mutagenesis and synthetic analogs of the peptide to probe the molecular determinants of channel binding and specificity. These efforts enhance understanding of peptide-ion channel interactions at the atomic level and inform the rational design of novel channel modulators with tailored properties.
Electrophysiological assay development: Jingzhaotoxin III is routinely incorporated into patch-clamp and other electrophysiological protocols to assess the functional impact of channel modulation. Its use as a reference compound or selective blocker in assay systems enables reliable validation of experimental models and screening platforms. The peptide's well-characterized effects on channel conductance support its role in standardizing and optimizing high-throughput screening assays for ion channel-targeted research.
Venom-derived peptide research: As a representative member of spider venom peptides, Jingzhaotoxin III contributes to the broader understanding of animal toxin diversity and evolution. Comparative analyses involving this toxin and related peptides aid in elucidating the structure-function relationships and evolutionary pressures that shape venom composition. Such studies not only expand the fundamental knowledge of toxin biology but also support the exploration of novel bioactive scaffolds for use in chemical biology and drug discovery initiatives.
Jingzhaotoxin-III (JZTX-III) is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao that inhibits Nav channels of rat cardiac myocytes by modifying voltage-dependent gating and also binds to Kv2.1 channel (Kd=0.43 μM) with an action model similar to that of hanatoxin1 and SGTx1. The solution structure of JZTX-III was determined by 1H 2D NMR method. The toxin adopts an ICK motif composed of three β-strands connected by four turns. Structural comparison of JZTX-III with those of other ICK motif peptides shows that they all adopt a conserved surface profile, a hydrophobic patch surrounded by charged residues, which might be the crucial site for voltage-gating ion channel inhibition. Furthermore, the similar action model of JZTX-III affecting both Kv and Nav channels implies that JZTX-III recognized a conserved receptor within the voltage sensing domains, which is similar to that of hanatoxin1 binding to both Kv and Cav channels.
Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels
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