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Type: Artigo
Title: Shared structural determinants for the calcium-independent liposome membrane permeabilization and sarcolemma depolarization in bothropstoxin-I, a LYS49-PLA(2) from the venom of bothrops jararacussu
Author: Aragão, Elisangela Aparecida
Randazzo-Moura, Priscila
Rostelato-Ferreira, Sandro
Rodrigues-Simioni, Léa
Ward, Richard. J.
Abstract: The structural determinants of myotoxicity of bothropstoxin-I (BthTX-I), a Lys49 phospholipase A2 from Bothrops jararacussu venom, were studied by measuring the resting membrane potential in the mouse phrenic nerve-diaphragm preparation. This method proved to be around 100-fold more sensitive than the creatine kinase release assay, and was used to evaluate a total of 31 site-directed BthTX-I alanine scanning mutants. Mutants that reduced the resting membrane potential were located in a surface patch defined by residues in the C-terminal loop (residues 115–129), positions 37–39 in the membrane interfacial recognition surface (Y46 and K54), and residue K93. These results expand the known structural determinants of the biological activity as evaluated by previous creatine kinase release experiments. Furthermore, a strong correlation is observed between the structural determinants of sarcolemma depolarization and calcium-independent disruption of liposome membranes, suggesting that a common mechanism of action underlies the permeabilization of the biological and model membranes
Subject: Mutagênese
Country: Reino Unido
Editor: Elsevier
Rights: Fechado
Identifier DOI: 10.1016/j.biocel.2009.08.016
Date Issue: 2009
Appears in Collections:FCM - Artigos e Outros Documentos

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