Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism

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dc.contributor.authorFernandes, Carlos A.H. [UNESP]
dc.contributor.authorPazin, Wallance M.
dc.contributor.authorDreyer, Thiago R. [UNESP]
dc.contributor.authorBicev, Renata N.
dc.contributor.authorCavalcante, Walter L.G. [UNESP]
dc.contributor.authorFortes-Dias, Consuelo L.
dc.contributor.authorIto, Amando S.
dc.contributor.authorOliveira, Cristiano L.P.
dc.contributor.authorFernandez, Roberto Morato [UNESP]
dc.contributor.authorFontes, Marcos R.M. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionFundação Ezequiel Dias (FUNED)
dc.date.accessioned2018-12-11T17:31:41Z
dc.date.available2018-12-11T17:31:41Z
dc.date.issued2017-03-03
dc.description.abstractCrotoxin (CTX) is the main neurotoxin found in Crotalus durissus rattlesnake venoms being composed by a nontoxic and non-enzymatic component (CA) and a toxic phospholipase A2 (CB). Previous crystallographic structures of CTX and CB provided relevant insights: (i) CTX structure showed a 1:1 molecular ratio between CA and CB, presenting three tryptophan residues in the CA/CB interface and one exposed to solvent; (ii) CB structure displayed a tetrameric conformation. This study aims to provide further information on the CTX mechanism of action by several biophysical methods. Our data show that isolated CB can in fact form tetramers in solution; however, these tetramers can be dissociated by CA titration. Furthermore, CTX exhibits a strong reduction in fluorescence intensity and lifetime compared with isolated CA and CB, suggesting that all tryptophan residues in CTX may be hidden by the CA/CB interface. By companying spectroscopy fluorescence and SAXS data, we obtained a new structural model for the CTX heterodimer in which all tryptophans are located in the interface, and the N-terminal region of CB is largely exposed to the solvent. Based on this model, we propose a toxic mechanism of action for CTX, involving the interaction of N-terminal region of CB with the target before CA dissociation.en
dc.description.affiliationDepartamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista UNESP
dc.description.affiliationDepartamento de Física Faculdade de Filosofia Ciências e Letras de Ribeirão Preto USP
dc.description.affiliationDepartamento de Física Experimental Instituto de Física Universidade de São Paulo - USP
dc.description.affiliationDepartamento de Farmacologia Instituto de Ciências Biológicas UFMG
dc.description.affiliationDiretoria de Pesquisa e Desenvolvimento Fundação Ezequiel Dias (FUNED)
dc.description.affiliationUnespDepartamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista UNESP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCAPES: 063/2011
dc.description.sponsorshipIdCAPES: 1592/2011
dc.description.sponsorshipIdFAPESP: 2013/17864-8
dc.description.sponsorshipIdFAPESP: 2014/26859-7
dc.description.sponsorshipIdFAPESP: 2015/17286-0
dc.description.sponsorshipIdCNPq: 300596/2013-8
dc.description.sponsorshipIdCNPq: 300908/2012-1
dc.description.sponsorshipIdCNPq: 304981/2012-5
dc.identifierhttp://dx.doi.org/10.1038/srep43885
dc.identifier.citationScientific Reports, v. 7.
dc.identifier.doi10.1038/srep43885
dc.identifier.file2-s2.0-85014608984.pdf
dc.identifier.issn2045-2322
dc.identifier.lattes3818330672146716
dc.identifier.scopus2-s2.0-85014608984
dc.identifier.urihttp://hdl.handle.net/11449/178695
dc.language.isoeng
dc.relation.ispartofScientific Reports
dc.relation.ispartofsjr1,533
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.titleBiophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanismen
dc.typeArtigo
unesp.author.lattes3818330672146716[9]

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Artigos - Física e Biofísica - IBB