title: Unraveling the processing and activation of snake venom metalloproteinases.
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 prodomain, but the processing of SVMPs is still unclear. In this study, we attempted to identify the presence of prodomain 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 prodomain, bands of zymogen molecular mass and prodomain 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. Prodomain 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 prodomain processing and degradation for controlling the activity of metalloproteinases.
authors.affiliation: Laboratório de Imunopalogia, ‡Laboratório de Farmacologia, §Laboratório de Biologia Celular, ∥Laboratório de Herpetologia, Instituto Butantan , São Paulo, São Paulo 05503-900, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Portes-Junior
authors.forename: Norma
authors.initials: N
authors.lastname: Yamanouye
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Carneiro
authors.forename: Paloma S
authors.initials: PS
authors.lastname: Knittel
authors.forename: Sávio S
authors.initials: SS
authors.lastname: Sant'Anna
authors.forename: Fabio C S
authors.initials: FC
authors.lastname: Nogueira
authors.forename: Magno
authors.initials: M
authors.lastname: Junqueira
authors.forename: Geraldo S
authors.initials: GS
authors.lastname: Magalhães
authors.forename: Gilberto B
authors.initials: GB
authors.lastname: Domont
authors.forename: Ana M
authors.initials: AM
authors.lastname: Moura-da-Silva
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017837:Bothrops / Q000033:anatomy & histology / Q000378:metabolism; D003435:Crotalid Venoms / Q000201:enzymology*; D004789:Enzyme Activation; D005088:Exocrine Glands / Q000166:cytology / Q000201:enzymology; D005260:Female; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D030162:Reptilian Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D003435:Crotalid Venoms; D011498:Protein Precursors; D030162:Reptilian Proteins; D045726:Metalloproteases