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dc.creatorPaiva, Owen K.
dc.creatorPla Ferrer, Davinia
dc.creatorWright, Christine E.
dc.creatorBeutler, Markus
dc.creatorSanz, Libia
dc.creatorGutiérrez, José María
dc.creatorWilliams, David J.
dc.creatorCalvete Chornet, Juan José
dc.date.accessioned2017-06-16T21:41:12Z
dc.date.available2017-06-16T21:41:12Z
dc.date.issued2014-10-14
dc.identifier.citationhttp://www.sciencedirect.com/science/article/pii/S1874391914003807
dc.identifier.issn1874-3919
dc.identifier.urihttps://hdl.handle.net/10669/30129
dc.description.abstractThe venom arsenal of the New Guinea small-eyed snake, Micropechis ikaheka, was investigated by a joint cDNA sequencing and venomics approach. Twenty-seven full-length DNA sequences encoding novel venom proteins were recovered in this study. Using this cDNA dataset we achieved locus-specific resolution for 19 out of the approximately 50 reverse-phase- and SDS-PAGE-separated venom proteins. The venom proteome of M. ikaheka is dominated by at least 29 D49-phospholipase A2 (PLA2) and 14 short and long neurotoxins of the three-finger toxin (3FTx) family. These protein classes represent, respectively, 80% and 9.2% of the total venom proteins. Two PIII-metalloproteinase (SVMP) molecules (7.6%), three CRISP isoforms (1.8%), and a single Kunitz-type inhibitor, vespryn, 5′-nucleotidase, serine proteinase and LAO molecules, none of which represents more than 0.7% of the total venom proteome, complete the protein arsenal of M. ikaheka. In concordance with clinical observations, this venom composition points to a central role for post-synaptically-acting neurotoxic toxins in the envenomation strategy developed by this species. PLA2 molecules represent the main myotoxic components of M. ikaheka venom. In addition, the estimated LD50 for mice of the reverse-phase-isolated 3FTx (0.22 mg/kg) and PLA2 (1.62 mg/kg) enriched fractions, strongly suggests that these two toxin classes contribute synergistically to venom lethality, with the 3FTxs playing a dominant role. The high structural and functional conservation exhibited by M. ikaheka and Australian elapid venoms may underlay the positive clinical outcomes of envenoming resulting from bites by M. ikaheka that have been documented through the use of bioCSL polyvalent antivenom. Biological significance The poorly understood venom proteome of the New Guinea small-eyed snake, Micropechis ikaheka, a large and powerfully built elapid endemic to Papua New Guinea and Indonesian West Papua province, was investigated through a combined venomics and venom gland transcriptomics approach. Although M. ikaheka accounts for only a small proportion of snakebites on the mainland, 40% of snakebites on Karkar Island are attributed to bites by this snake. Major effects of envenomings include life-threatening post-synaptic neuromuscular blockade resulting in respiratory paralysis, myotoxicity, severe bleeding, hypotension and cardiovascular abnormalities. We have investigated the contribution of 3FTxs and PLA2 molecules in venom lethality, myotoxicity, and cardiovascular function. Our work provides important correlations between venom composition and its pharmacological activity. In conjunction with the antivenomics work reported in the companion paper, our study may contribute to improve treatment outcomes for snakebite victims of M. ikaheka.es_ES
dc.description.sponsorshipMinisterio de Ciencia e Innovación/[BFU2010-17373]// Españaes_ES
dc.description.sponsorshipGeneralitat Valenciana/[PROMETEO/2010/005]//Españaes_ES
dc.description.sponsorshipPrograma Iberoamericano de Ciencia y Tecnología para el Desarrollo/[BIOTOX P211RT 0412]/CYTED/Españaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[741-B2-652]/UCR/Costa Ricaes_ES
dc.language.isoen_USes_ES
dc.sourceJournal of Proteomics; Volumen 110. 2014es_ES
dc.subjectMicropechis ikahekaes_ES
dc.subjectSnake venomicses_ES
dc.subjectVenom gland cDNAes_ES
dc.subjectPharmacological effects of snake venomes_ES
dc.subjectThree-finger toxines_ES
dc.subjectPhospholipase A2es_ES
dc.titleCombined venom gland cDNA sequencing and venomics of the New Guinea small-eyed snake, Micropechis ikahekaes_ES
dc.typeartículo original
dc.identifier.doi10.1016/j.jprot.2014.07.019
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.codproyecto741-B2-652
dc.identifier.pmid25109465


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