title: Mass spectrometric analysis of the individual variability of Bothrops jararaca venom peptide fraction. Evidence for sex-based variation among the bradykinin-potentiating peptides.
abstract: Variation in the snake venom proteome is well documented and it is a ubiquitous phenomenon at all taxonomical levels. However, variation in the snake venom peptidome is so far not described. In this work we used mass spectrometry [liquid chromatography/mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOFMS)] to explore sex-based differences among the venom peptides of eighteen sibling specimens of Bothrops jararaca of a single litter born and raised in the laboratory. MALDI-TOFMS analyses showed individual variability among the bradykinin-potentiating peptides (BPPs), and, interestingly, four new peptides were detected only in female venoms and identified by de novo sequencing as cleaved BPPs lacking the C-terminal Q-I-P-P sequence. Similar results were obtained with venom from wild-caught adult non-sibling specimens of B. jararaca and in this case we were able to identify the gender of the specimen by analyzing the MALDI-TOF profile of the peptide fraction and finding the cleaved peptides only in female venoms. Synthetic replicates of the cleaved BPPs were less potent than the full-length BPP-10c in potentiating the bradykinin hypotensive effect, suggesting that the C-terminus is critical for the interaction of the BPPs with their mammalian molecular targets. This work represents a comprehensive mass spectrometric analysis of the peptide fraction of B. jararaca venom and shows for the first time sex-based differences in the snake venom peptidome of sibling and non-sibling snakes and suggests that the BPPs may follow distinct processing pathways in female and male individuals.
authors.affiliation: Laboratório Especial de Toxinologia Aplicada/CAT-CEPID, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo-SP 05503-900, Brazil.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pimenta
authors.forename: Benedito C
authors.initials: BC
authors.lastname: Prezoto
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Konno
authors.forename: Robson L
authors.initials: RL
authors.lastname: Melo
authors.forename: Maria F
authors.initials: MF
authors.lastname: Furtado
authors.forename: Antonio C M
authors.initials: AC
authors.lastname: Camargo
authors.forename: Solange M T
authors.initials: SM
authors.lastname: Serrano
mesh_terms: D000818:Animals; D017837:Bothrops / Q000378:metabolism*; D001920:Bradykinin / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003435:Crotalid Venoms / Q000737:chemistry*; D005260:Female; D008297:Male; D010449:Peptide Mapping / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein / Q000379:methods; D012737:Sex Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D003435:Crotalid Venoms; D010455:Peptides; D001920:Bradykinin