A post-translational modification perspective of Bothrops venom toxins: site-specific proteomic characterization of N-glycans and Cys residues.

• Grant number: 16/16935-7
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2016
• Effective date (End): October 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Solange Maria de Toledo Serrano
• Grantee: Débora Andrade Silva
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID
• Associated scholarship(s): 18/08794-0 - Analysis of the microheterogeneity in N- and O-glycosylation of snake toxins from Bothrops genus: identification of intact glycopeptides., BE.EP.DR

Abstract

Snake venoms are important biological fluids, used for predation and defense, which appeared during the development of the order Squamata and later evolved in a variable mode in the group of advanced snakes. The variability of their compositions can be observed in all taxonomical levels, however, the factors that drove and selected such features are still under discussion. The hypothesis of recruitment of expression in the venom of genes involved with physiological functions and the neofunctionalization of these genes in the venom is corroborated by comparative transcriptomic analyses between the venom gland and other snake organs. However, these analyses are based only in the comparison of the primary structures of the proteins and the product of their paralog genes, without taking into account the post-translational modifications present in these proteins. In this context, toxin glycosylation is abundant in viperid snake venoms and previous studies of our group on its role in speciation events, in the Bothrops genus, indicate its conservation during snake evolution, in parallel with other molecular markers that defined their phylogenetic classification. Nevertheless, accurate analyses about the distribution and occurrence of sites of N-glycosylation and O-glycosylation in snake venom glycoproteins are still missing. Thus, in this project we propose to identify by mass spectrometry the N- and O-glycosylation sites in glycoproteins of B. jararaca, B. alcatraz, B. insularis, B. fonsecai, B. cotiara, B. jararacussu and B. moojeni venoms, in order to evaluate their role in directing the toxins to their targets, and to compare these results to the phylogenetic classification of these species. We also propose: i) to evaluate the role of sialic acid present in glycoproteins of B. jararaca venom in their pathological effects; ii) to evaluate the role of glycans present in the substrates of bothropasin, a hemorrhagic metalloproteinase of B. jararaca venom, on its primary specificity.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANDRADE-SILVA, DEBORA; ZELANIS, ANDRE; TRAVAGLIA-CARDOSO, SILVIA R.; NISHIYAMA, JR., MILTON Y.; SERRANO, SOLANGE M. T.. Venom Profiling of the Insular Species Bothrops alcatraz: Characterization of Proteome, Glycoproteome, and N-Terminome Using Terminal Amine Isotopic Labeling of Substrates. JOURNAL OF PROTEOME RESEARCH, v. 20, n. 2, p. 1341-1358, FEB 5 2021. (13/13548-4, 16/16935-7, 13/07467-1, 13/14651-3)

DE FARIAS, IASMIM BAPTISTA; DE MORAIS-ZANI, KAREN; SERINO-SILVA, CAROLINE; SANT'ANNA, SAVIO S.; DA ROCHA, MARISA M. T.; GREGO, KATHLEEN F.; ANDRADE-SILVA, DEBORA; SERRANO, SOLANGE M. T.; TANAKA-AZEVEDO, ANITA M.. Functional and proteomic comparison of Bothrops jararaca venom from captive specimens and the Brazilian Bothropic Reference Venom. JOURNAL OF PROTEOMICS, v. 174, p. 36-46, MAR 1 2018. (17/16908-2, 13/05357-4, 17/01890-0, 13/07467-1, 14/11108-0, 16/16935-7)

ANDRADE-SILVA, DEBORA; NISHIYAMA JR, MILTON Y.; STUGINSKI, DANIEL R.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T.. The distinct N-terminomes of Bothrops jararaca newborn and adult venoms. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 7, JUL 2021. (16/16935-7, 13/07467-1, 13/14651-3)