Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity

Abstract

As more data are generated from proteome and transcriptome analyses of snake venoms, we are gaining an appreciation of the complexity of the venoms and, to some degree, the various sources of such complexity. However, our knowledge is still far from complete. The translation of genetic information from the snake genome to the transcriptome and ultimately the proteome is only beginning to be appreciated, and will require significantly more investigation of the snake venom genomic structure prior to a complete understanding of the genesis of venom composition. Venom complexity, however, is derived not only from the venom genomic structure but also from transcriptome generation and translation and, perhaps most importantly, post‐translation modification of the nascent venom proteome. In this review, we examine the snake venom metalloproteinases, some of the predominant components in viperid venoms, with regard to possible synthesis and post‐translational mechanisms that contribute to venom complexity. The aim of this review is to highlight the state of our knowledge on snake venom metalloproteinase post‐translational processing and to suggest testable hypotheses regarding the cellular mechanisms associated with snake venom metalloproteinase complexity in venoms.

Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

“…Venom complexity is further influenced by the effect of posttranslational protein modifications (34,35). Across the sampled species, we detected multiple instances of the same toxin being identified in distinct proteomic fractions (SI Appendix, Tables S1-S6), signifying the presence of multiple protein products as the result of proteolysis (SI Appendix, Fig.…”

“…These observations likely reflect (i) the proteolytic cleavage of single gene proteins forming multiple products (e.g., SVMPs; ref. 34) and (ii) the cleavage of multimeric structures, which can be encoded by the same gene or different genes from either the same or distinct toxin families (35). Considerable interspecific variation in the number of proteolysed toxins was observed, ranging from three genes in E. p. leakeyi producing six venom protein products, to 13 forming 36 in B. arietans venom (SI Appendix, Fig.…”

Vesicle-associated Membrane Protein (VAMP) Cleavage by a New Metalloprotease from the Brazilian Scorpion Tityus serrulatus

“…The primary structure of the isolated venom protease is not found in existing amino acid sequence data bases. While our biochemical characterization is in development, the scorpion venom metalloprotease, antarease, is composed of 245 residues and is therefore distinguished from snake venom metalloproteinases that comprise more than 400 residues (46). The antarease sequence has been included in the Swiss Protein data base Uniprot with accession number P86392.…”

Action of neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi venom, on skeletal muscle: an ultrastructural and immunocytochemistry study

“…These enzymes are part of the metzincins superfamily, a diverse and expansive group of zinc peptidases from both prokaryotes and eukaryotes (5,6). SVMPs are synthesized as multidomain zymogen proteins and are grouped in classes and subclasses from P-I to P-III according to their domain organization (7). SVMPs from P-I class are composed in the mature form only of the catalytic domain and are generally fibrinogenolytic and weak hemorrhagic enzymes.…”

“…SVMPs from P-III class are frequently potent hemorrhagins that consist of a catalytic domain followed by disintegrin-like and cysteine-rich domains, linked via the carboxy-terminal to the catalytic domain. P-I and P-III SVMPs are the most abundant group in viper venoms which conserve the catalytic domain in the mature form (7).…”