title: Snake venomics of Crotalus tigris: the minimalist toxin arsenal of the deadliest Nearctic rattlesnake venom. Evolutionary Clues for generating a pan-specific antivenom against crotalid type II venoms [corrected].
abstract: We report the proteomic and antivenomic characterization of  Crotalus tigris  venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7-8 gene products from 6 toxin families; the presynaptic β-neurotoxic heterodimeric PLA(2), Mojave toxin, and two serine proteinases comprise, respectively, 66 and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1-2 PIII-SVMPs each represent 0.1-5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend toward neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by pedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris,  Crotalus horridus ,  Crotalus oreganus  helleri,  Crotalus scutulatus  scutulatus, and  Sistrurus catenatus  catenatus indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South and North American Crotalus species.
authors.affiliation: Departamento de Biotecnología, Universidad Politécnica de Valencia, Valencia, Spain. jcalvete@ibv.csic.es
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
authors.forename: Alicia
authors.initials: A
authors.lastname: Pérez
authors.forename: Bruno
authors.initials: B
authors.lastname: Lomonte
authors.forename: Elda E
authors.initials: EE
authors.lastname: Sánchez
authors.forename: Libia
authors.initials: L
authors.lastname: Sanz
mesh_terms: D000818:Animals; D000997:Antivenins / Q000737:chemistry* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D003435:Crotalid Venoms / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology / Q000633:toxicity; D017839:Crotalus / Q000378:metabolism*; D007163:Immunosorbent Techniques; D051379:Mice; D009498:Neurotoxins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D009500:Neutralization Tests; D010802:Phylogeny; D020543:Proteome / Q000032:analysis / Q000737:chemistry; D040901:Proteomics; D011817:Rabbits
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; D009498:Neurotoxins; D020543:Proteome