7LVN

Solution structure of tarantula toxin omega-Avsp1a

Summary for 7LVN

• Entry DOI: 10.2210/pdb7lvn/pdb
• NMR Information: BMRB: 30872
• Descriptor: Omega-Avsp1a (1 entity in total)
• Functional Keywords: toxin, disulfide-rich peptide, inhibitor cystine knot, tarantular toxin, calcium channel inhibitor
• Biological source: Avicularia sp. AVIC29FPM
• Total number of polymer chains: 1
• Total formula weight: 4239.85

Authors

Chin, Y.K.Y.,Herzig, V.,King, G.F. (deposition date: 2021-02-26, release date: 2022-03-02, Last modification date: 2024-11-20)

Primary citation

Herzig, V.,Chen, Y.C.,Chin, Y.K.,Dekan, Z.,Chang, Y.W.,Yu, H.M.,Alewood, P.F.,Chen, C.C.,King, G.F.
The Tarantula Toxin omega-Avsp1a Specifically Inhibits Human Ca V 3.1 and Ca V 3.3 via the Extracellular S3-S4 Loop of the Domain 1 Voltage-Sensor.
Biomedicines, 10:-, 2022

PubMed Abstract: Inhibition of T-type calcium channels (Ca3) 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 Ca3. However, subtype-specific Ca3 inhibitors for therapeutic purposes or for studying the physiological roles of Ca3 subtypes are missing. To bridge this gap, we employed our spider venom library and uncovered that ("Amazonas Purple", Peru) tarantula venom inhibited specific T-type Ca 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 Ca3.1 and Ca3.3, but only 25% of Ca3.2 currents. In order to investigate the toxin binding site, we generated a range of chimeric channels from the less sensitive Ca3.2 and more sensitive Ca3.3. Our results suggest that domain-1 of Ca3.3 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.

PubMed: 35625803
DOI: 10.3390/biomedicines10051066

Experimental method

SOLUTION NMR