AUTHOR=Alvarado Diana , Cardoso-Arenas Samuel , Corrales-García Ligia-Luz , Clement Herlinda , Arenas Iván , Montero-Dominguez Pavel Andrei , Olamendi-Portugal Timoteo , Zamudio Fernando , Csoti Agota , Borrego Jesús , Panyi Gyorgy , Papp Ferenc , Corzo Gerardo 

TITLE=A Novel Insecticidal Spider Peptide that Affects the Mammalian Voltage-Gated Ion Channel hKv1.5

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.563858

DOI=10.3389/fphar.2020.563858

ISSN=1663-9812

ABSTRACT=<p>Spider venoms include various peptide toxins that modify the ion currents, mainly of excitable insect cells. Consequently, scientific research on spider venoms has revealed a broad range of peptide toxins with different pharmacological properties, even for mammal species. In this work, thirty animal venoms were screened against hK<sub>v</sub>1.5, a potential target for atrial fibrillation therapy. The whole venom of the spider <italic>Oculicosa supermirabilis</italic>, which is also insecticidal to house crickets, caused voltage-gated potassium ion channel modulation in hK<sub>v</sub>1.5. Therefore, a peptide from the spider <italic>O. supermirabilis</italic> venom, named Osu1, was identified through HPLC reverse-phase fractionation. Osu1 displayed similar biological properties as the whole venom; so, the primary sequence of Osu1 was elucidated by both of N-terminal degradation and endoproteolytic cleavage. Based on its primary structure, a gene that codifies for Osu1 was constructed <italic>de novo</italic> from protein to DNA by reverse translation. A recombinant Osu1 was expressed using a pQE30 vector inside the <italic>E. coli</italic> SHuffle expression system. recombinant Osu1 had voltage-gated potassium ion channel modulation of human hK<sub>v</sub>1.5, and it was also as insecticidal as the native toxin. Due to its novel primary structure, and hypothesized disulfide pairing motif, Osu1 may represent a new family of spider toxins.</p>