Origin of Functional Diversities in Taiwan Banded Krait (Bungarus multicinctus) Three-finger Proteins

Abstract

Taiwan banded krait (Bungarus multicinctus) neurotoxins and neurotoxin homologues, including α-bungarotoxin (Bgt), κ-Bgt, γ-Bgt, BM8, BM10-1, BM10-2 and BM14, have been reported. These proteins have a common three-finger scaffold and conserved cysteine residues at homologous positions. Nevertheless, these proteins show functional diversity and sequence variations in loop regions. The genomic DNAs encoding the precursors of α-Bgt, κ-Bgt, γ-Bgt, BM10-1 and BM14 are organized with three exons and two introns. The intron regions of these genes have a high degree of sequence identity, but the protein-coding regions are highly variable with the exception of the signal peptide region. These findings suggest that B. multicinctus three-finger proteins share a common evolutionary origin, and the evolution of snake venom proteins shows a tendency to diversify their functions, which may be beneficial for catching prey. Given that a multitude of functional diversities is noted with three-finger toxins, protein engineering in highly variable regions without distorting the three-finger scaffold may result in the development biopharmaceutical agents with novel functions of scientific and therapeutic interest.