Molecular Diversity of Box Jellyfish Toxins

Box jellyfish (cubozoans) are renowned for their ability to immobilise and kill prey and inflict painful and debilitating stings to humans by injecting potent venoms from their nematocysts. Chironex fleckeri is the largest species of box jellyfish and its venom produces extremely rapid and potentially life-threatening effects. Advances in box jellyfish toxinology using bioactivity-guided purification methods, tandem mass spectrometry and molecular cloning techniques have revealed that C. fleckeri venom contains a diverse array of proteins that is dominated by a family of abundant high molecular weight venom proteins that are cytolytic, cytotoxic and cause profound cardiovascular collapse in experimental animals. Related toxins with similar biological activities are present in other jellyfish species and comparative analysis of available toxin sequences infers that this expanding family of potent cnidarian toxins forms at least two distinct protein clades. Sequence divergence among family members coupled with experimental evidence suggests there are significant structural variations between clades that may alter their function and target specificity. In this context, an overview of this unique family of protein toxins is presented, including a brief history of their discovery and recent progress in their purification and molecular characterisation primarily from a bioinformatic perspective.