Proteomic analysis of the proteolytic activity of HF3, a metalloproteinase from the venom of Bothrops jararaca, upon human and snake plasma.

• Grant number: 11/16623-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Solange Maria de Toledo Serrano
• Grantee: Luciana Bertholim Nasciben
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 98/14307-9 - Center for Applied Toxinology, AP.CEPID

Abstract

Proteinases are present in the venoms of many snakes and are structurally classified into trypsin-like serine proteinases (SVSPs) and metalloproteinases (SVMPs). SVMPs are found mainly in viperid venoms and are important players in the local hemorrhage and pro-inflammatory pathogenesis observed upon envenomation. SVMPs are classified in three main classes depending on the organization of their domains (P-I, P-II and P-III). They are members of the Reprolysin subfamily of metalloproteinases, which also includes two groups of homologous proteins, ADAMs and ADMTs. The P-III class of SVMPs and the ADAMs/ADAMTs share homologous disintegrin-like (D) and cysteine-rich (C) domains. This structural similarity has guided a number of functional assays currently employed in toxinology studies. HF3 is a P-III classSVMP, which is extremely hemorrhagic, and shows a minimum hemorrhagic dose of 240 fmol on the rabbit skin. Although SVMPs are highly active against mammalian tissues, they do not affect the venom components or the venom gland tissue. One of the aims of this project is to evaluate the substrate repertoire (degradome) of HF3 on human plasma in vitro, using proteomics methodologies. Moreover, the peptide bond cleavage specificity of HF3 will be analyzed using a peptide library derived from human blood plasma. Comparatively, the degradomics of HF3 will be also analyzed using Bothrops jararaca plasma. The results of this study will serve as basis to understand the hemorrhagic effects of HF3, as well as the complex physiopathological process generated by SVMPs that involves the cleavage of plasma proteins.

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)

BERTHOLIM, LUCIANA; CHAVES, ALISON F. A.; OLIVEIRA, ANA K.; MENEZES, MILENE C.; ASEGA, AMANDA F.; TASHIMA, ALEXANDRE K.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T.. Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins. TOXINS, v. 13, n. 11, NOV 2021. (11/08514-8, 20/12317-2, 11/16623-1, 13/07467-1)

ASEGA, AMANDA F.; BARROS, BIANCA C. S. C.; CHAVES, ALISON F. A.; OLIVEIRA, ANA K.; BERTHOLIM, LUCIANA; KITANO, EDUARDO S.; SERRANO, SOLANGE M. T.. Mouse skin peptidomic analysis of the hemorrhage induced by a snake venom metalloprotease. Amino Acids, v. 55, n. 9, p. 17-pg., 2023-06-30. (21/10570-5, 13/07467-1, 20/12317-2, 10/17328-0, 11/11308-0, 11/16623-1, 10/00206-0)

BERTHOLIM, LUCIANA; ZELANIS, ANDRE; OLIVEIRA, ANA K.; SERRANO, SOLANGE M. T.. Proteome-derived peptide library for the elucidation of the cleavage specificity of HF3, a snake venom metalloproteinase. Amino Acids, v. 48, n. 5, p. 1331-1335, MAY 2016. (13/07467-1, 11/16623-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

NASCIBEN, Luciana Bertholim. Proteomic analysis of the proteolytic activity of HF3, a metalloproteinase from the venom of Bothrops jararaca, upon human and snake plasma. 2014. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.