Study of the degradome of HF3, a PIII-class snake venom metalloproteinase from Bothrops jararaca venom, on cultured fibroblasts

Abstract

Proteinases are the major components of viperid venom proteomes. In this context, snake venom metalloproteinases (SVMPs) are among the most abundant enzymes found in venoms and are responsible for several of the pathological effects of envenomation. The structural similarity of SVMPs with ADAMs (A Disintegrin and Metalloproteinase) and ADAMTSs (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) has guided a number of functional assays currently employed in toxinology studies. The study of SVMPs activities in complex biological systems with the use of omics technologies has allowed the evaluation of several aspects of the pathology of the ophidian envenomation, as well as the signaling pathways triggered by SVMPs. Using isotopic terminal amine labeling of proteins and mass spectrometry analysis, the main goal of this project is to evaluate the proteolytic specificity of the metalloproteinase HF3 upon a peptide library derived from secreted proteins of cultured fibroblasts. The results obtained by such approach will serve as basis for the understanding of the repertoire of substrates of HF3 as well as will complement others approaches currently developed in the post doctoral project. (AU)