Label-Free (XIC)
Quantification of Venom Procoagulant
and Neurotoxin Expression in Related Australian Elapid Snakes Gives
Insight into Venom Toxicity Evolution
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Abstract
This
study demonstrates a direct role of venom protein expression
alteration in the evolution of snake venom toxicity. Avian skeletal
muscle contractile response to exogenously administered acetylcholine
is completely inhibited upon exposure to South Australian and largely
preserved following exposure to Queensland eastern brown snake <i>Pseudonaja textilis</i> venom, indicating potent postsynaptic
neurotoxicity of the former and lack thereof of the latter venom.
Label-free quantitative proteomics reveals extremely large differences
in the expression of postsynaptic three-finger α-neurotoxins
in these venoms, explaining the difference in the muscle contractile
response and suggesting that the type of toxicity induced by venom
can be modified by altered expression of venom proteins. Furthermore,
the onset of neuromuscular paralysis in the rat phrenic nerve-diaphragm
preparation occurs sooner upon exposure to the venom (10 μg/mL)
with high expression of α-neurotoxins than the venoms containing
predominately presynaptic β-neurotoxins. The study also finds
that the onset of rat plasma coagulation is faster following exposure
to the venoms with higher expression of venom prothrombin activator
subunits. This is the first quantitative proteomic study that uses
extracted ion chromatogram peak areas (MS1 XIC) of distinct homologous
tryptic peptides to directly show the differences in the expression
of venom proteins