Structures of N-Glycans of Bothrops Venoms Revealed as Molecular Signatures that Contribute to Venom Phenotype in Viperid Snakes

Autor(es)

Andrade-Silva, Debora ^[1] ; Ashline, David ^[2] ; Tran, Thuy ^[2] ; Lopes, Aline Soriano ^[3] ; Travaglia Cardoso, Silvia Regina ^[4] ; Reis, Marcelo da Silva ^[5] ; Zelanis, Andre ^[6] ; Serrano, Solange M. T. ^[1] ; Reinhold, Vernon ^[2]

Afiliação do(s) autor(es)

^[1] Univ New Hampshire, Lab Especial Toxinol Aplicad, Durham, NH 03824 - USA

^[2] Univ New Hampshire, Glyc Ctr, Durham, NH 03824 - USA

^[3] Univ Fed Sao Paulo, Dept Quim, Inst Ciencias Ambientais Quim & Farmaceut, BR-09913030 Diadema - Brazil

^[4] Inst Butantan, Museu Biol, BR-05503900 Sao Paulo - Brazil

^[5] Inst Butantan, Lab Especial Ciclo Celular, Ctr Toxins Immune Response & Cell Signaling CeTIC, BR-05503900 Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo ICT UNIFESP, Inst Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR & CELLULAR PROTEOMICS; v. 17, n. 7, p. 1261-1284, JUL 2018.
• Citações Web of Science: 3

Resumo

The complexity of snake venoms has long been investigated to explore a myriad of biologically active proteins and peptides that are used for immobilizing or killing prey, and are responsible for the pathological effects observed on envenomation. Glycosylation is the main post-translational modification (PTM) of viperid venoms but currently there is little understanding of how protein glycosylation impacts the variation of venom proteomes. We have previously reported that Bothrops venom glycoproteomes contain a core of components that markedly define their composition and parallel their phylogenetic classification. Here we extend those observations to eight Bothrops species evaluating the N-glycomes by LC-MS as assigned cartoon structures and detailing those structures separately as methylated analogs using ion-trap mass spectrometry (MSn). Following ion disassembly through multiple steps provided sequence and linkage isomeric details that characterized 52 unique compositions in Bothrops venoms. These occurred as 60 structures, of which 26 were identified in the venoms of the Jararaca Complex (B. alcatraz, B. insularis, and B. jararaca), 20 in B. erythromelas, B. jararacussu, B. moojeni and B. neuwiedi venoms, and 22 in B. cotiara venom. Further, quantitative analysis of these N-glycans showed variable relative abundances in the venoms. For the first time a comprehensive set of N-glycan structures present in snake venoms are defined. Despite the fact that glycosylation is not template-defined, the N-glycomes of these venoms mirror the phylogeny cladograms of South American bothropoid snakes reported in studies on morphological, molecular data and feeding habits, exhibiting distinct molecular signatures for each venom. Considering the complexity of N-glycan moieties generally found in glycoproteins, characterized by different degrees of branching, isomer structures, and variable abundances, our findings point to these factors as another level of complexity in Bothrops venoms, features that could dramatically contribute to their distinct biological activities. (AU)

• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/12245-0 - Glicômica aplicada à caracterização de venenos do gênero Bothrops
• Beneficiário: Débora Andrade Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Mestrado
• Processo FAPESP: 13/14651-3 - Abordagens experimentais em proteômica e glicômica aplicadas à caracterização do veneno de Bothrops alcatraz
• Beneficiário: Débora Andrade Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/13548-4 - Caracterização proteômica / glicoproteômica de venenos de serpentes do complexo Bothrops jararaca com ênfase no N-terminoma e N-glicoma de toxinas
• Beneficiário: Solange Maria de Toledo Serrano
• Modalidade de apoio: Auxílio à Pesquisa - Regular