title: Venomics of the Australian eastern brown snake (Pseudonaja textilis): Detection of new venom proteins and splicing variants.
abstract: The eastern brown snake is the predominant cause of snakebites in mainland Australia. Its venom induces defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia. Cardiovascular collapse has been described as an early cause of death in patients, but, so far, the mechanisms involved have not been fully identified. In the present work, we analysed the venome of Pseudonaja textilis by combining high throughput proteomics and transcriptomics, aiming to further characterize the components of this venom. The combination of these techniques in the analysis and identification of toxins, venom proteins and putative toxins allowed the sequence description and the identification of the following: prothrombinase coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and "acidic PLA2", three-finger toxins (3FTx) and the Kunitz-type protease inhibitor textilinin, venom metalloproteinase, C-type lectins, cysteine rich secretory proteins, calreticulin, dipeptidase 2, as well as evidences of Heloderma lizard peptides. Deep data-mining analysis revealed the secretion of a new transcript variant of venom coagulation factor 5a and the existence of a splicing variant of PLA2 modifying the UTR and signal peptide from a same mature protein. The transcriptome revealed the diversity of transcripts and mutations, and also indicates that splicing variants can be an important source of toxin variation.
authors.affiliation: Centro de Biotecnologia, IPEN, Av. Lineu Prestes 2242, 05508-000, São Paulo, SP, Brazil.
authors.forename: Vincent Louis
authors.initials: VL
authors.lastname: Viala
authors.affiliation: Institut für Klinische Chemie, Universitätsklinikum Hamburg-Eppendorf, Haus Ost 26, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Hildebrand
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Trusch
authors.affiliation: Centro de Biotecnologia, IPEN, Av. Lineu Prestes 2242, 05508-000, São Paulo, SP, Brazil.
authors.forename: Tamara Mieco
authors.initials: TM
authors.lastname: Fucase
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Juliana Mozer
authors.initials: JM
authors.lastname: Sciani
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Daniel Carvalho
authors.initials: DC
authors.lastname: Pimenta
authors.affiliation: Departamento de Física, IBILCE, UNESP, Rua Cristóvão Colombo, 2265 15054-000, São José do Rio Preto, SP, Brazil.
authors.forename: Raghuvir K
authors.initials: RK
authors.lastname: Arni
authors.affiliation: Institut für Klinische Chemie, Universitätsklinikum Hamburg-Eppendorf, Haus Ost 26, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Betzel
authors.affiliation: Venom Supplies Pty. Ltd., PO Box 547, 5352, Tanunda, South Australia, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mirtschin
authors.affiliation: Venom Supplies Pty. Ltd., PO Box 547, 5352, Tanunda, South Australia, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Dunstan
authors.affiliation: Centro de Biotecnologia, IPEN, Av. Lineu Prestes 2242, 05508-000, São Paulo, SP, Brazil. Electronic address: pspencer@ipen.br.
authors.forename: Patrick Jack
authors.initials: PJ
authors.lastname: Spencer
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001315:Australia; D004546:Elapid Venoms / Q000737:chemistry*; D017815:Elapidae; D020869:Gene Expression Profiling; D040901:Proteomics; D030162:Reptilian Proteins / Q000737:chemistry* / Q000302:isolation & purification; D020539:Sequence Analysis, Protein
chemical_list: D004546:Elapid Venoms; D030162:Reptilian Proteins
keywords: Proteome; Pseudonaja textilis; Splicing variant; Toxin; Transcriptome