Characterization of Neuwiedin, a new disintegrin from Bothrops neuwiedi venom gland with distinct cysteine pattern

Author(s)

Lima-dos-Santos, I. ^[1] ; Della-Casa, M. S. ^[1] ; Portes-Junior, J. A. ^[1] ; Calabria, P. A. L. ^[1] ; Magalhaes, G. S. ^[1] ; Moura-da-Silva, A. M. ^[1]

Affiliation

^[1] Inst Butantan, Lab Imunopatol, BR-05503900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Toxicon; v. 104, p. 57-64, SEP 15 2015.
• Web of Science Citations: 4

Abstract

Disintegrins are cysteine-rich toxins containing the RGD motif exposed in a loop that binds integrins such as alpha(IIb)beta(3,) alpha(5)beta(1) and alpha(v)beta(3). The flexibility of the RGD loop, controlled by the profile of the cysteine pairs and the residues flanking the RGD sequence, are key structural features for the functional activity of these molecules. Recently, our group reported a transcript in the venom gland of Bothrops neuwiedi corresponding to a new P-II SVMP precursor, BnMPIIx, in which the RGD-binding loop includes many substituted residues and unique cysteine residues at the C-terminal. In this paper, we obtained the recombinant disintegrin domain of BnMPIlx, Neuwiedin, which inhibited ADP-induced platelet aggregation, endothelial cell adhesion to fibrinogen and tube formation in Matrigel with no particular selectivity to alpha(IIb)beta(3) or endothelial cell integrins. This value was also comparable to the inhibition observed with other recombinant disintegrins with conserved cysteine positions and residues in RGD loop. In this regard, Neuwiedin is an important component to understand the functional relevance of the diversity generated by accelerated evolution of venom toxins as well as to find out eventual new disintegrin-dependent targets that may be approached with disintegrins. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/16277-9 - Variability in venom composition of Bothrops snakes and functional relevance of the presence of distinct metaloproteinases in venom composition
• Grantee: Ana Maria Moura da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/13559-8 - BNMP2-III, a novel metalloproteinase from Bothrops neuwiedi venom:Production of recombinant form and its effects in hemostasis.
• Grantee: Isa Lima dos Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/26058-8 - Inhibition of mammalian and snake venom metalloproteinases by the recombinant pro-domain of jararhagin and its relevant peptide fragments
• Grantee: Ana Maria Moura da Silva
• Support Opportunities: Regular Research Grants