On the quaternary structure of taipoxin and textilotoxin: The advantage of being multiple

Many presynaptic neurotoxins endowed with a phospholipase A2 activity are produced by a variety of snake species (Harris, 1991; Kini, 1997). These toxins have evolved from PLA2 enzymes mainly implicated in digestive functions (Davidson and Dennis, 1990). The evolutionary transition from a hydrolytic enzyme to a toxin has been achieved without significant modifications to the stable multi-disulfide-bridged protein PLA2 scaffold, apart from the loss of the so-called “pancreatic loop” (Alape-Girón et al., 1999; Kini, 1997). Rather, subsequent mutations have generated the ability of some of these toxins to bind and act at the presynaptic membrane of motoneurons end plates (Fletcher and Jiang, 1995). This evolution has been driven by a very strong selection pressure, as prey immobilisation greatly improves the extent of feeding and therefore the fitness of the toxin-producing species. The acquisition of neurospecific binding properties by mutation and selection is at the basis of the transformation of a generic PLA2 enzyme into a presynaptic neurotoxin as it concentrates their phospholipid hydrolytic activity within selected portions of the plasma membrane, whose alteration results in loss of neurotransmission (Kini and Evans, 1989; Fletcher and Jiang, 1995; Kini, 2003). The ensuing change of membrane structure and the increased permeability to Ca2+ causes a sustained blockade of the transmission of the nerve impulse to the muscle ( [Rigoni et al., 2005] and [Rigoni et al., 2007]; Rossetto and Montecucco, 2008).