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AutorScorsato, Valéria
AutorLima, Tatiani B
AutorRigheto, Germanna Lima
AutorZanchin, Nilson Ivo Tonin
AutorBrandão-Neto, José
AutorSandy, James
AutorPereira, Humberto D'muniz
AutorFerrari, Állan J. R.
AutorGozzo, Fabio C.
AutorSmetana, Juliana H. C.
AutorAparicio, Ricardo
Fecha de acceso2017-07-26T14:29:12Z
Fecha de disponibilización2017-07-26T14:29:12Z
Fecha de publicación2016
ReferenciaSCORSATO, Valéria et al. Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus. Scientific Reports, v. 6, p. 1-12, Aug. 2016.pt_BR
ISSN2045-2322pt_BR
URIhttps://www.arca.fiocruz.br/handle/icict/20410
Idiomaporpt_BR
EditorNature Publishing Grouppt_BR
Derechos de autoropen accesspt_BR
Palabras clave en PortuguésElementos Estruturais de Proteínaspt_BR
TítuloCrystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUSpt_BR
Tipo del documentoArticlept_BR
DOI10.1038/srep30813pt_BR
Resumen en InglésTOR signaling pathway regulator-like (TIPRL) is a regulatory protein which inhibits the catalytic subunits of Type 2A phosphatases. Several cellular contexts have been proposed for TIPRL, such as regulation of mTOR signaling, inhibition of apoptosis and biogenesis and recycling of PP2A, however, the underlying molecular mechanism is still poorly understood. We have solved the crystal structure of human TIPRL at 2.15Å resolution. The structure is a novel fold organized around a central core of antiparallel beta-sheet, showing an N-terminal α/β region at one of its surfaces and a conserved cleft at the opposite surface. Inside this cleft, we found a peptide derived from TEV-mediated cleavage of the affinity tag. We show by mutagenesis, pulldown and hydrogen/deuterium exchange mass spectrometry that this peptide is a mimic for the conserved C-terminal tail of PP2A, an important region of the phosphatase which regulates holoenzyme assembly, and TIPRL preferentially binds the unmodified version of the PP2A-tail mimetic peptide DYFL compared to its tyrosine-phosphorylated version. A docking model of the TIPRL-PP2Ac complex suggests that TIPRL blocks the phosphatase’s active site, providing a structural framework for the function of TIPRL in PP2A inhibition.pt_BR
AfiliaciónInstitute of Chemistry, University of Campinas, Campinas, SP, Brazil. / Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, SP, Brazil. / Institute of Biology, University of Campinas, Campinas, SP, Brazil.pt_BR
AfiliaciónInstitute of Chemistry, University of Campinas, Campinas, SP, Brazil. / Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, SP, Brazil.pt_BR
AfiliaciónBrazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, SP, Brazil.pt_BR
AfiliaciónFundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.pt_BR
AfiliaciónDiamond Light Source, Chilton, UK.pt_BR
AfiliaciónDiamond Light Source, Chilton, UK.pt_BR
AfiliaciónPhysics Institute of São Carlos, University of São Paulo, São Carlos, SP, Brazil.pt_BR
AfiliaciónInstitute of Chemistry, University of Campinas, Campinas, SP, Brazil.pt_BR
AfiliaciónInstitute of Chemistry, University of Campinas, Campinas, SP, Brazil.pt_BR
AfiliaciónBrazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, SP, Brazil.pt_BR
AfiliaciónInstitute of Chemistry, University of Campinas, Campinas, SP, Brazil.pt_BR
Palavras clave en InglêsProtein Phosphatase 2pt_BR
Palavras clave en InglêsProtein Structural Elementspt_BR
Palavras clave en InglêsMass Spectrometrypt_BR
Palavras claveProteína Fosfatasa 2pt_BR
Palavras claveElementos Estructurales de las Proteínaspt_BR
Palavras claveEspectrometría de Masaspt_BR
DeCSProteína Fosfatase 2pt_BR
DeCSEspectrometria de Massaspt_BR


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