Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution.
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 Pseudonaja textilis 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.
Department of Biochemistry and Molecular Biology, BIO21 Institute, University of Melbourne , 30 Flemington Road, Parkville, Victoria 3010, Australia.|Monash Venom Group, Department of Pharmacology, Monash University , 9 Ancora Imparo Way, Clayton, Victoria 3800, Australia.
Jure
J
Skejic
Monash Biomedical Proteomics Facility, Monash University , 23 Innovation Walk, Clayton, Victoria 3800, Australia.
David L
DL
Steer
Venom Supplies Pty Ltd. , Stonewell Road, Tanunda, South Australia 5352, Australia.
Nathan
N
Dunstan
Monash Venom Group, Department of Pharmacology, Monash University , 9 Ancora Imparo Way, Clayton, Victoria 3800, Australia.
Wayne C
WC
Hodgson
D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D001717:Birds; D003029:Coagulants / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D019295:Computational Biology / Q000379:methods; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004546:Elapid Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D017815:Elapidae / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity; D010446:Peptide Fragments / Q000737:chemistry* / Q000302:isolation & purification; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D013045:Species Specificity; D014357:Trypsin / Q000737:chemistry
D003029:Coagulants; D004546:Elapid Venoms; D009498:Neurotoxins; D010446:Peptide Fragments; D012697:Serine Endopeptidases; C505354:prothrombin activator protease, Pseudonaja textilis; D014357:Trypsin
Oxyuranus scutellatus; Pseudonaja textilis; evolution; label-free quantification; neurotoxins; procoagulants; proteome; quantitative proteomics; snake venom; toxicity