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The Tarantula Toxin ω-Avsp1a Specifically Inhibits Human CaV3.1 and CaV3.3 via the Extracellular S3-S4 Loop of the Domain 1 Voltage-Sensor3.44 MB
Published VersionCC BY V4.0, Open Access
Journal article
The Tarantula Toxin ω-Avsp1a Specifically Inhibits Human CaV3.1 and CaV3.3 via the Extracellular S3-S4 Loop of the Domain 1 Voltage-Sensor
Biomedicines, Vol.10(5), pp.1-17
2022
Abstract
Inhibition of T-type calcium channels (CaV3) prevents development of diseases related to cardiovascular and nerve systems. Further, knockout animal studies have revealed that some diseases are mediated by specific subtypes of CaV3. However, subtype-specific CaV3 inhibitors for therapeutic purposes or for studying the physiological roles of CaV3 subtypes are missing. To bridge this gap, we employed our spider venom library and uncovered that Avicularia spec. (“Amazonas Purple”, Peru) tarantula venom inhibited specific T-type CaV channel subtypes. By using chromatographic and mass-spectrometric techniques, we isolated and sequenced the active toxin ω-Avsp1a, a C-terminally amidated 36 residue peptide with a molecular weight of 4224.91 Da, which comprised the major peak in the venom. Both native (4.1 μM) and synthetic ω-Avsp1a (10 μM) inhibited 90% of CaV3.1 and CaV3.3, but only 25% of CaV3.2 currents. In order to investigate the toxin binding site, we generated a range of chimeric channels from the less sensitive CaV3.2 and more sensitive CaV3.3. Our results suggest that domain-1 of CaV3.3 is important for the inhibitory effect of ω-Avsp1a on T-type calcium channels. Further studies revealed that a leucine of T-type calcium channels is crucial for the inhibitory effect of ω-Avsp1a.
Details
- Title
- The Tarantula Toxin ω-Avsp1a Specifically Inhibits Human CaV3.1 and CaV3.3 via the Extracellular S3-S4 Loop of the Domain 1 Voltage-Sensor
- Authors
- Volker Herzig (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringYong-Cyung Chen (Author) - Academia SinicaYanni K Y Chin (Author) - The University of QueenslandZoltan Dekan (Author) - The University of QueenslandYu-Wang Chang (Author) - Academia SinicaHui-Ming Yu (Author) - Academia SinicaPaul F Alewood (Author) - The University of QueenslandChien-Chang Chen (Author) - Academia SinicaGlenn F King (Author) - The University of Queensland
- Publication details
- Biomedicines, Vol.10(5), pp.1-17
- Publisher
- MDPI AG
- Date published
- 2022
- DOI
- 10.3390/biomedicines10051066
- ISSN
- 2227-9059
- Copyright note
- Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99635579102621
- Output Type
- Journal article
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