title: Structural and phylogenetic studies with MjTX-I reveal a multi-oligomeric toxin--a novel feature in Lys49-PLA2s protein class.
abstract: The mortality caused by snakebites is more damaging than many tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease. For this reason, snakebite envenoming adversely affects health services of tropical and subtropical countries and is recognized as a neglected disease by the World Health Organization. One of the main components of snake venoms is the Lys49-phospholipases A2, which is catalytically inactive but possesses other toxic and pharmacological activities. Preliminary studies with MjTX-I from Bothrops moojeni snake venom revealed intriguing new structural and functional characteristics compared to other bothropic Lys49-PLA2s. We present in this article a comprehensive study with MjTX-I using several techniques, including crystallography, small angle X-ray scattering, analytical size-exclusion chromatography, dynamic light scattering, myographic studies, bioinformatics and molecular phylogenetic analyses.Based in all these experiments we demonstrated that MjTX-I is probably a unique Lys49-PLA2, which may adopt different oligomeric forms depending on the physical-chemical environment. Furthermore, we showed that its myotoxic activity is dramatically low compared to other Lys49-PLA2s, probably due to the novel oligomeric conformations and important mutations in the C-terminal region of the protein. The phylogenetic analysis also showed that this toxin is clearly distinct from other bothropic Lys49-PLA2s, in conformity with the peculiar oligomeric characteristics of MjTX-I and possible emergence of new functionalities in response to environmental changes and adaptation to new preys.
authors.affiliation: Depto de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista-UNESP, Botucatu, SP, Brazil.
authors.forename: Guilherme H M
authors.initials: GH
authors.lastname: Salvador
authors.forename: Carlos A H
authors.initials: CA
authors.lastname: Fernandes
authors.forename: Angelo J
authors.initials: AJ
authors.lastname: Magro
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Marchi-Salvador
authors.forename: Walter L G
authors.initials: WL
authors.lastname: Cavalcante
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Fernandez
authors.forename: Márcia
authors.initials: M
authors.lastname: Gallacci
authors.forename: Andreimar M
authors.initials: AM
authors.lastname: Soares
authors.forename: Cristiano L P
authors.initials: CL
authors.lastname: Oliveira
authors.forename: Marcos R M
authors.initials: MR
authors.lastname: Fontes
mesh_terms: D000818:Animals; D017837:Bothrops; D002850:Chromatography, Gel; D003435:Crotalid Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009119:Muscle Contraction / Q000187:drug effects; D010316:Particle Size; D054467:Phospholipases A2 / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010802:Phylogeny; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D030162:Reptilian Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D053838:Scattering, Small Angle
chemical_list: D003435:Crotalid Venoms; D030162:Reptilian Proteins; D054467:Phospholipases A2; D008239:Lysine