Sialic acid-containing glycans play a role in the activity of snake venom proteases

Author(s)

Bras-Costa, Carolina ; Chaves, Alison Felipe Alencar ; Trevisan-Silva, Dilza ; Menezes, Milene C. ; Rocha, Marisa M. T. ; Cajado-Carvalho, Daniela ; Andrade-Silva, Debora ; Serrano, Solange M. T.

• Document type: Journal article
• Source: Biochimie; v. 204, p. 14-pg., 2023-01-07.

Abstract

Structural variability is a feature of snake venom proteins, and glycosylation is a post-translational modification that contributes to the diversification of venom proteomes. Studies by our group have shown that Bothrops venoms are distinctly defined by their glycoprotein content, and that most hybrid/ complex N-glycans identified in these venoms contain sialic acid. Considering that metalloproteases and serine proteases are abundant components of Bothrops venoms and essential in the envenomation process, and that these enzymes contain several glycosylation sites, the role of sialic acid in venom proteolytic activity was evaluated. Here we show that removal of sialic acid by treatment of nine Bothrops venoms with neuraminidase (i) altered the pattern of gelatinolysis in zymography of most venoms and reduced the gelatinolytic activity of all venoms, (ii) decreased the proteolytic activity of some venoms on fibrinogen and the clotting activity of human plasma of all venoms, and (iii) altered the proteolysis profile of plasma proteins by B. jararaca venom, suggesting that sialic acid may play a role in the interaction of proteases with their protein substrates. In contrast, the profile of venom amidolytic activity on Bz-Arg-pNA did not change after removal of sialic acid, indicating that this monosaccharide is not essential in N- glycans of serine proteases acting on small substrates. In summary, these results expand the knowledge about the variability of the subproteomes of Bothrops venom proteases, and for the first time point to the importance of carbohydrate chains containing sialic acid in the enzymatic activities of venom proteases relevant in human envenomation.(c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• FAPESP's process: 13/13548-4 - Proteomic/Glycoproteomic characterization of the venoms of the Bothrops jararaca complex with emphasis on the N-terminome and N-glycome of toxins
• Grantee: Solange Maria de Toledo Serrano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/23017-1 - Analysis of the complexity of venom glycoproteomes of Bothrops genus
• Grantee: Carolina Brás Costa
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/09929-3 - Bothrops snake venoms: impact of glycosylation on the complexity of proteomes and toxins function
• Grantee: Carolina Brás Costa
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)