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dc.contributor.authorFiorillo, Annarita
dc.contributor.authordi Marino, Daniele
dc.contributor.authorBertuccini, Lucia
dc.contributor.authorVia, Allegra
dc.contributor.authorPozio, Edoardo
dc.contributor.authorCamerini, Serena
dc.contributor.authorIlari, Andrea
dc.contributor.authorLalle, Marco
dc.date.accessioned2016-02-21T08:51:21Z
dc.date.available2016-02-21T08:51:21Z
dc.date.issued2014-03-21
dc.identifier.citationFiorillo A, di Marino D, Bertuccini L, Via A, Pozio E, et al. (2014) The Crystal Structure of Giardia duodenalis 14-3-3 in the Apo Form: When Protein Post-Translational Modifications Make the Difference. PLoS ONE 9: e92902. Available: http://dx.doi.org/10.1371/journal.pone.0092902.
dc.identifier.issn1932-6203
dc.identifier.pmid24658679
dc.identifier.doi10.1371/journal.pone.0092902
dc.identifier.urihttp://hdl.handle.net/10754/596823
dc.description.abstractThe 14-3-3s are a family of dimeric evolutionary conserved pSer/pThr binding proteins that play a key role in multiple biological processes by interacting with a plethora of client proteins. Giardia duodenalis is a flagellated protozoan that affects millions of people worldwide causing an acute and chronic diarrheal disease. The single giardial 14-3-3 isoform (g14-3-3), unique in the 14-3-3 family, needs the constitutive phosphorylation of Thr214 and the polyglycylation of its C-terminus to be fully functional in vivo. Alteration of the phosphorylation and polyglycylation status affects the parasite differentiation into the cyst stage. To further investigate the role of these post-translational modifications, the crystal structure of the g14-3-3 was solved in the unmodified apo form. Oligomers of g14-3-3 were observed due to domain swapping events at the protein C-terminus. The formation of filaments was supported by TEM. Mutational analysis, in combination with native PAGE and chemical cross-linking, proved that polyglycylation prevents oligomerization. In silico phosphorylation and molecular dynamics simulations supported a structural role for the phosphorylation of Thr214 in promoting target binding. Our findings highlight unique structural features of g14-3-3 opening novel perspectives on the evolutionary history of this protein family and envisaging the possibility to develop anti-giardial drugs targeting g14-3-3.
dc.description.sponsorshipThis study has been partially supported by the Italian Ministero dell'Istruzione, dell'Universita e della Ricerca (FIRB grant RBFR08F41U), Istituto Superiore di Sanita (1APC/1303/2011), Fondazione Istituto Italiano di Tecnologia (IIT), (grant "Tecniche di Bioinformatica strutturale: Modellizzazione di proteine, docking e simulazione di dinamica molecolare), and the King Abdullah University of Science and Technology (KAUST, grant KUK-I1-012-43). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.publisherPublic Library of Science (PLoS)
dc.rightsThis is an open-access article distributed under the terms of the , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subject.meshModels, Molecular
dc.titleThe crystal structure of Giardia duodenalis 14-3-3 in the apo form: when protein post-translational modifications make the difference.
dc.typeArticle
dc.identifier.journalPLoS ONE
dc.identifier.pmcidPMC3962474
dc.contributor.institutionDepartment of Biochemical Sciences "A. Rossi-Fanelli", University of Rome "Sapienza", Rome, Italy; Institute of Molecular Biology and Pathology, CNR, Rome, Italy and Institute Pasteur Cenci-Bolognetti Foundation at Department of Biochemical Sciences "A. Rossi-Fanelli", University of Rome "Sapienza", Rome, Italy.
dc.contributor.institutionDepartment of Physics, University of Rome "Sapienza", Rome, Italy.
dc.contributor.institutionDepartment of Health and Technology, Istituto Superiore di Sanità, Rome, Italy.
dc.contributor.institutionDepartment of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
dc.contributor.institutionDepartment of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
dc.contributor.institutionInstitute of Molecular Biology and Pathology, CNR, Rome, Italy and Institute Pasteur Cenci-Bolognetti Foundation at Department of Biochemical Sciences "A. Rossi-Fanelli", University of Rome "Sapienza", Rome, Italy.
kaust.grant.numberKUK-I1-012-43
refterms.dateFOA2018-06-13T14:20:32Z


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