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Voltage-gated sodium channels are critical for the generation and propagation of action potentials. Gating modifier toxins from spider venom can modulate the gating mechanism of sodium channels and thus have potential as drug leads. Here, we established expression of the gating modifier toxin PaurTx-3, a sodium channel inhibitor found in the venom of the spider Phrixotrichus auratus. Whole-cell voltage-clamp recordings indicated that recombinant PaurTx-3 (rPaurTx-3) inhibited Nav1.4, Nav1.5, and Nav1.7 currents with IC 50 values of 61 nM, 72 nM, and 25 nM, respectively. Furthermore, rPaurTx-3 irreversibly inhibited Nav1.7 currents, but had 60-70% recovery in Nav1.4 and Nav1.5 after washing with a bath solution. rPaurTx-3 also hyperpolarized the voltage-dependent steady-state inactivation curve and significantly slowed recovery from fast inactivation of Nav1.7. Current-clamp recordings showed that rPaurTx-3 suppressed small DRG neuron activity. The biological activity assay findings for rPaurTx-3 support its potent pharmacological effect in Nav1.7 and small DRG neurons., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study investigated geographic variability in the venom of Centruroides sculpturatus scorpions from different biotopes. Venom from scorpions collected from two different regions in Arizona; Santa Rita Foothills (SR) and Yarnell (Yar) were analyzed. We found differences between venoms, mainly in the two most abundant peptides; SR (CsEv2e and CsEv1f) and Yar (CsEv2 and CsEv1c) identified as natural variants of CsEv1 and CsEv2. Sequence analyses of these peptides revealed conservative amino acid changes between variants, which may underlie biological activity against arthropods. A third peptide (CsEv6) was highly abundant in the Yar venom compared to the SR venom. CsEv6 is a 67 amino acid peptide with 8 cysteines. CsEv6 did not exhibit toxicity to the three animal models tested. However, both venoms shared similarities in peptides that are predicted to deter predators. For example, both venoms expressed CsEI (lethal to chick) in similar abundance, while CsEd and CsEM1a (toxic to mammals) displayed only moderate variation in their abundance. Electrophysiological evaluation of CsEd and CsEM1a showed that both toxins act on the human sodium-channel subtype 1.6 (hNav 1.6). Complete sequencing revealed that both toxins are structurally similar to beta-toxins isolated from different Centruroides species that also target hNav 1.6., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: House dust mites are an important source of indoor allergens. More than 30 allergens of Dermatophagoides farinae (D. farinae) have been identified. Yet there may be many other allergens in mites remain to be characterized., Methods: α-Tubulin (also named Der f 33) was cloned, expressed and purified. Reaction to specific-IgE, skin prick test and a mouse asthma model were employed to determine the allergenicity of Der f 33., Results: The recombinant Der f 33 reacted to the serum of patients with mite allergy. The positive rate of skin prick test (SPT) was 23.5%. In an asthma mouse model, Der f 33 induced the airway allergy-like responses. Moreover, serum specific IgE and IgG1, interleukin-4 (IL-4) from bronchoalveolar lavage fluid (BALF) and spleen cell culture supernatant were markedly increased. In addition, Der f 33 upregulated the CD80 and TNF-α levels in dendritic cells (DCs)., Conclusions: Der f 33 is a novel allergen of D. farinae. It modulates the functions of DCs and induces airway allergy., (Copyright © 2016. Published by Elsevier GmbH.)

The eggs of black widow spider (L. tredecimguttatus) have been demonstrated to be rich in biologically active components that exhibit great research value and application foreground. In the present study, a protein toxin, named Latroeggtoxin-II, was isolated from the eggs using the combination of gel filtration, ion exchange chromatography and reversed-phase high performance liquid chromatography. Electrospray mass spectrometric analysis indicated that the molecular weight of the protein was 28.69 kDa, and Edman degradation revealed that its N-terminal sequence was ESIQT STYVP NTPNQ KFDYE VGKDY-. After being abdominally injected into mice and P. americana, the protein could make the animals especially P. americana display a series of poisoning symptoms. Electrophysiological experiments demonstrated that the protein could selectively inhibit tetrodotoxin-resistant Na(+) channel currents in rat dorsal root ganglion neurons, without significant effect on the tetrodotoxin-sensitive Na(+) channel currents. Using multiple proteomic strategies, the purified protein was shown to have only a few similarities to the existing proteins in the databases, suggesting that it was a novel protein isolated from the eggs of black widow spiders., (Copyright © 2014. Published by Elsevier B.V.)