Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein: structural basis for the high specificity of exfoliative toxins

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorMariutti, Ricardo B.
dc.creatorSouza, Tatiana A. C. B.
dc.creatorUllah, Anwar
dc.creatorCaruso, Icaro P.
dc.creatorMoraes, Fábio R. de
dc.creatorZanphorlin, Leticia M.
dc.creatorTartaglia, Natayme R.
dc.creatorSeyffert, Nubia
dc.creatorAzevedo, Vasco A.
dc.creatorLe Loir, Yves
dc.creatorMurakami, Mário T.
dc.creatorArni, Raghuvir K.
dc.date2015-12-07T15:40:37Z
dc.date2016-10-25T21:24:08Z
dc.date2015-12-07T15:40:37Z
dc.date2016-10-25T21:24:08Z
dc.date2015-11-06
dc.date.accessioned2017-04-06T09:32:49Z
dc.date.available2017-04-06T09:32:49Z
dc.identifierBiochemical And Biophysical Research Communications, v. 467, n. 1, p. 171-117, 2015.
dc.identifier1090-2104
dc.identifierhttp://hdl.handle.net/11449/131689
dc.identifierhttp://acervodigital.unesp.br/handle/11449/131689
dc.identifier10.1016/j.bbrc.2015.08.083
dc.identifier26299923
dc.identifierhttp://dx.doi.org/10.1016/j.bbrc.2015.08.083
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/942229
dc.descriptionExfoliative 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.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científco e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageeng
dc.publisherElsevier B. V.
dc.relationBiochemical And Biophysical Research Communications
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCrystal structure
dc.subjectExfoliative toxin d-like protein
dc.subjectStaphylococcus aureus
dc.subjectToxin-mediated staphylococcal syndromes
dc.titleCrystal structure of Staphylococcus aureus exfoliative toxin D-like protein: structural basis for the high specificity of exfoliative toxins
dc.typeOtro


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