Crystal structure of [i]Staphylococcus aureus[/i] exfoliative toxin D-like protein: Structural basis for the high specificity of exfoliative toxins.
2015
Mariutti, Ricardo B | Souza, Tatiana a C B | Ullah, Anwar | Caruso, Icaro P | de Moraes, Fábio R | Zanphorlin, Leticia M | Rocha Tartaglia, Natayme | Seyffert, Nubia | Azevedo, Vasco A | Le Loir, Yves | Murakami, Mário T | Arni, Raghuvir K | Department of Physics, IBILCE/UNESP ; Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP) | Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ) ; Pasteur Network (Réseau International des Instituts Pasteur) | Bioethanol Science and Technology Laboratory (CTBE) ; National Center for Research in Energy and Materials | Science et Technologie du Lait et de l'Oeuf (STLO) ; Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST | Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas ; Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG) | Brazilian Biosciences National Laboratory (LNBio) ; National Center for Research in Energy and Materials | CNPq, FAPESP, CAPES and Institut National de la Recherche Agronomique (INRA/France
Exfoliative toxins are serine proteases secreted by Staphylococcus aureus that are associated with toxin-mediated staphylococcal syndromes. To date, four different serotypes of exfoliative toxins have been identified and 3 of them (ETA, ETB, and ETD) are linked to human infection. Among these toxins, only the ETD structure remained unknown, limiting our understanding of the structural determinants for the functional differentiation between these toxins. We recently identified an ETD-like protein associated to S. aureus strains involved in mild mastitis in sheep. The crystal structure of this ETD-like protein was determined at 1.95 Å resolution and the structural analysis provide insights into the oligomerization, stability and specificity and enabled a comprehensive structural comparison with ETA and ETB. Despite the highly conserved molecular architecture, significant differences in the composition of the loops and in both the N- and C-terminal α-helices seem to define ETD-like specificity. Molecular dynamics simulations indicate that these regions defining ET specificity present different degrees of flexibility and may undergo conformational changes upon substrate recognition and binding. DLS and AUC experiments indicated that the ETD-like is monomeric in solution whereas it is present as a dimer in the asymmetric unit indicating that oligomerization is not related to functional differentiation among these toxins. Differential scanning calorimetry and circular dichroism assays demonstrated an endothermic transition centered at 52 °C, and an exothermic aggregation in temperatures up to 64 °C. All these together provide insights about the mode of action of a toxin often secreted in syndromes that are not associated with either ETA or ETB.
Afficher plus [+] Moins [-]Informations bibliographiques
Cette notice bibliographique a été fournie par Institut national de la recherche agronomique
Découvrez la collection de ce fournisseur de données dans AGRIS