Combinatorial chemistry in toad: a protoxin self-resistance way to its
own bufadienolide toxin
Abstract
1. Toxin resistance in all taxa is important for their survival.
Resistance to bufadienolide toxin is mediated by molecular changes to
the sodium-potassium-pump. As for toads themselves, the parotid is
consisted of extremely high concentration of bufadienolide toxin, it
indicates toads need stronger resistance for self-protection than any
other species involved in toad predation. Thus, besides the widespread
convergence of Na+/K+-ATPase, toads may develop a unique self-resistance
way for their accumulated bufadienolide toxin. 2. Our studies on
invasive cane toads from Australia and common asiatic toads from China
showed that toads store defensive venom in parotid as a combinatorial
library composed of low-toxic protoxin (conjugated bufadienolides),
which is characterized by two building blocks, i.e. high-toxic toxin
(free bufadienolide) and the argininyl side chain contributed to toxin
absorption promotion. This protoxin could be hydrolyzed to high-toxic
toxin for defense immediately as it is discharged from parotid at the
time when toad is attacked or stimulated by predators. 3. Our results
revealed that toads indeed develop a unique protoxin self-resistance way
to their own extremely high concentration of bufadienolide toxin for
self-protection besides the widespread convergence of Na+/K+-ATPase. The
revelation of this protoxin self-resistance way highlights the
importance and ecological multifunctionality of the sophisticated
combinatorial chemistry of nature and may partly account for the strong
adaptability of toad as infamous ailing invaders. It completes the
picture of self-resistance mechanism to their own bufadienolide toxin
for toad or may even for many other venomous animals.