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
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
Departamento de Alimentos, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia, Medellín, Colombia.
Front Pharmacol. 2021 Jan 13;11:563858. doi: 10.3389/fphar.2020.563858. eCollection 2020.
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 hK1.5, a potential target for atrial fibrillation therapy. The whole venom of the spider , which is also insecticidal to house crickets, caused voltage-gated potassium ion channel modulation in hK1.5. Therefore, a peptide from the spider 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 from protein to DNA by reverse translation. A recombinant Osu1 was expressed using a pQE30 vector inside the SHuffle expression system. recombinant Osu1 had voltage-gated potassium ion channel modulation of human hK1.5, 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.
蜘蛛毒液包含多种肽毒素,这些毒素主要作用于可兴奋的昆虫细胞,改变其离子电流。因此,对蜘蛛毒液的科学研究揭示了大量具有不同药理特性的肽毒素,甚至对哺乳动物也有作用。在这项研究中,针对心房颤动治疗的潜在靶点hK1.5,对30种动物毒液进行了筛选。对家蟋蟀也具有杀虫作用的蜘蛛全毒液,可对hK1.5产生电压门控钾离子通道调节作用。因此,通过高效液相色谱反相分级分离,从蜘蛛毒液中鉴定出一种名为Osu1的肽。Osu1表现出与全毒液相似的生物学特性;于是,通过N端降解和内切蛋白酶切割确定了Osu1的一级序列。基于其一级结构,通过反向翻译从蛋白质到DNA构建了编码Osu1的基因。使用pQE30载体在SHuffle表达系统中表达重组Osu1。重组Osu1对人hK1.5具有电压门控钾离子通道调节作用,并且与天然毒素一样具有杀虫作用。由于其新颖的一级结构和推测的二硫键配对基序,Osu1可能代表一种新的蜘蛛毒素家族。