Interaction and cleavage of cell and plasma proteins by the platelet-aggregating serine protease PA-BJ of Bothrops jararaca venom

Author(s)

Cajado-Carvalho, Daniela ; Morone, Mariana S. L. C. ; da Ros, Nancy ; Serrano, Solange M. T.

• Document type: Journal article
• Source: Biochimie; v. 232, p. 6-pg., 2025-05-01.

Abstract

PA-BJ is a serine protease present in Bothrops jararaca venom that triggers platelet aggregation and granule secretion by activating the protease-activated receptors PAR-1 and PAR-4, without clotting fibrinogen. These receptors also have a relevant role in endothelial cells, however, the interaction of PA-BJ with other membrane-bound or soluble targets is not known. Here we explored the activity of PA-BJ on endothelial cell receptor, cytoskeleton, and coagulation proteins in vitro, and show the degradation of fibrinogen and protein C, and the limited proteolysis of actin, EPCR, PAR-1, and thrombomodulin. Antithrombin, factors XI and XIII and protein S were not cleaved by PA-BJ. Moreover, using surface plasmon resonance PA-BJ was demonstrated to bind to actin, EPCR, fibrinogen, PAR-1, and thrombomodulin, with dissociation constants (KD) in the micromolar range. Considering that these proteins play critical roles in pathways of blood coagulation and maintenance of endothelium integrity, their binding and cleavage by PA-BJ could contribute to the alterations in hemostasis and cell permeability observed in B. jararaca envenomation process. (c) 2025 Elsevier B.V. and Soci & eacute;t & eacute; Fran & ccedil;aise de Biochimie et Biologie Mol & eacute;culaire (SFBBM). All rights are reserved, including those for text and data mining, AI training, and similar technologies. (AU)

• FAPESP's process: 17/19252-0 - Proteomic analysis of the effects of PA-BJ, a serine proteinase of Bothrops jararaca venom, upon peripheral blood endothelial cell culture
• Grantee: Daniela Cajado de Oliveira Souza Carvalho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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