Citation

Portes-Junior JA, Yamanouye N, Carneiro SM, Knittel PS, Sant'Anna SS, Nogueira FC, Junqueira M, Magalhães GS, Domont GB, Moura-da-Silva AM. J. Proteome Res. 2014; 13(7): 3338-3348.

Copyright

(Copyright © 2014, American Chemical Society)

DOI

10.1021/pr500185a

PMID

24914619

Abstract

Snake venom metalloproteinases (SVMPs) are zinc-dependent enzymes responsible for most symptoms of human envenoming. Like matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase (ADAM) proteins, SVMPs are synthesized as zymogens, and enzyme activation is regulated by hydrolysis of their pro-domain, but the processing of SVMPs is still unclear. In this study, we attempted to identify the presence of pro-domain in different compartments of snake venom glands as zymogens or in the free form, to elucidate some mechanism involved in SVMP activation. Using antibodies obtained by immunization with a recombinant pro-domain, bands of zymogen molecular mass and pro-domain peptides were detected mostly in gland extracts all along the venom production cycle and in the venom collected from the lumen at the peak of venom production. Pro-domain was detected in secretory cells mostly in the secretory vesicles near the Golgi. We hypothesize that the processing of SVMPs starts within secretory vesicles and continues in the lumen of the venom gland just after enzyme secretion, and involves different steps compared to ADAMs and MMPs, but can be used as a model for studying the relevance of peptides resulting from pro-domain processing and degradation for controlling the activity of metalloproteinases.

Language: en