Sequence analysis and 3-dimensional molecular modelling of Heteroscorpine from the venom of Heterometrus spp

• Published in: Maejo international journal of science and technology 2018-09, Vol.12 (3), p.187-198
• Main Authors: Incamnoi, Paroonkorn, Patramanon, Rina, Klaynongsruang, Sompong, Chaveerach, Arunrat, Bunyatratchata, Wandee, Uawonggul, Nunthawun, Sukprasert, Sophida, Namonsai, Teerawat, Noikotr, Kowit, Rungsa, Prapenpuksiri, Daduang, Jureerut, Daduang, Sakda
• Format: Article
• Language: English
• Subjects: Amino acids; Bioinformatics; Cell walls; Cysteine; Defensins; Deoxyribonucleic acid; Dimensional analysis; DNA; Ethanol; Gene expression; Genes; Genomics; Insects; Membranes; Molecular modelling; Peptides; Phenols; Polymerase chain reaction; Potassium channels; Proteins; Residues; Software; Spectrum analysis; Three dimensional models; Toxins; Venom; α-Toxin
• ISSN: 1905-7873; 1905-7873

Based on the recently identified sequence of Heteroscorpine-1 (HS-1), the genes encoding the scorpine family of toxins from three Heterometrus spp. in Thailand were amplified by polymerase chain reactions (PCR). All three genomic DNAs encoded a precursor protein consisting of 95 amino acid residues, and these proteins share a highly conserved structure with other known scorpion long-chain K+-channel toxins. Based on the data obtained from our specimens, all scorpine family genes possess a 5 UTR and a region encoding the putative signal peptide. The six cysteine positions are highly conserved in invertebrate defensins and scorpion K+ channel toxins, suggesting the presence of a common three-dimensional structure with a cysteine-stabilised αβ (CSαβ) motif. Our scorpine gene family contains an intron that is completely identical to the known scorpion K+-channel blockers in size, consensus junctions, putative branch point, and A + T abundance. We used α-toxin (PDB i.d. 4hhf.1.A), toxin II (PDB i.d.laho.l.A) and defensin (PDB i.d. 2b68.1) as templates in our analysis of 3-dimensional structures. Residues Asn48 - Lys55 of the mature Heteroscorpine sequence form the α-helix, residues Lys60 - His64 form β-sheet 1, and residues Lys67 - Gly71 form β-sheet 2. Heteroscorpine is predicted to have this structure due to the presence of 3 disulphide bridges. The structure completely follows the typical Cys pattern of invertebrate defensins (CX4-16CX2HCX6-9GX1CX4-9CX1C). Thus, the scorpine family of toxins is likely to use the same mechanism to penetrate the bacterial cell wall as defensin peptides from other insect families.