Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/20410 |
Resumo: | Institute 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. |
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Scorsato, ValériaLima, Tatiani BRigheto, Germanna LimaZanchin, Nilson Ivo ToninBrandão-Neto, JoséSandy, JamesPereira, Humberto D'munizFerrari, Állan J. R.Gozzo, Fabio C.Smetana, Juliana H. C.Aparicio, Ricardo2017-07-26T14:29:12Z2017-07-26T14:29:12Z2016SCORSATO, 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. 2016.2045-2322https://www.arca.fiocruz.br/handle/icict/2041010.1038/srep30813porNature Publishing GroupElementos Estruturais de ProteínasProtein Phosphatase 2Protein Structural ElementsMass SpectrometryProteína Fosfatasa 2Elementos Estructurales de las ProteínasEspectrometría de MasasProteína Fosfatase 2Espectrometria de MassasCrystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUSinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInstitute 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.Institute of Chemistry, University of Campinas, Campinas, SP, Brazil. / Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, SP, Brazil.Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, SP, Brazil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Diamond Light Source, Chilton, UK.Diamond Light Source, Chilton, UK.Physics Institute of São Carlos, University of São Paulo, São Carlos, SP, Brazil.Institute of Chemistry, University of Campinas, Campinas, SP, Brazil.Institute 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 Chemistry, University of Campinas, Campinas, SP, Brazil.TOR 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/20410/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCrystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus.pdfCrystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus.pdfapplication/pdf2132858https://www.arca.fiocruz.br/bitstream/icict/20410/2/Crystal%20structure%20of%20the%20human%20Tip41%20orthologue%2c%20TIPRL%2c%20reveals%20a%20novel%20fold%20and%20a%20binding%20site%20for%20the%20PP2Ac%20C-terminus.pdff3c011ca732ddc9cb6872d8a9f79a48cMD52TEXTCrystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus.pdf.txtCrystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus.pdf.txtExtracted texttext/plain56997https://www.arca.fiocruz.br/bitstream/icict/20410/3/Crystal%20structure%20of%20the%20human%20Tip41%20orthologue%2c%20TIPRL%2c%20reveals%20a%20novel%20fold%20and%20a%20binding%20site%20for%20the%20PP2Ac%20C-terminus.pdf.txt4549e97004e081a9d6c5d34789940da3MD53icict/204102018-08-15 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| dc.title.pt_BR.fl_str_mv |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| title |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| spellingShingle |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS Scorsato, Valéria Elementos Estruturais de Proteínas Protein Phosphatase 2 Protein Structural Elements Mass Spectrometry Proteína Fosfatasa 2 Elementos Estructurales de las Proteínas Espectrometría de Masas Proteína Fosfatase 2 Espectrometria de Massas |
| title_short |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| title_full |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| title_fullStr |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| title_full_unstemmed |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| title_sort |
Crystal Structure of the human TIP41 Orthologue, TIPRL, reveals a novel fold and a binding site for the PP2AC C-TERMINUS |
| author |
Scorsato, Valéria |
| author_facet |
Scorsato, Valéria Lima, Tatiani B Righeto, Germanna Lima Zanchin, Nilson Ivo Tonin Brandão-Neto, José Sandy, James Pereira, Humberto D'muniz Ferrari, Állan J. R. Gozzo, Fabio C. Smetana, Juliana H. C. Aparicio, Ricardo |
| author_role |
author |
| author2 |
Lima, Tatiani B Righeto, Germanna Lima Zanchin, Nilson Ivo Tonin Brandão-Neto, José Sandy, James Pereira, Humberto D'muniz Ferrari, Állan J. R. Gozzo, Fabio C. Smetana, Juliana H. C. Aparicio, Ricardo |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Scorsato, Valéria Lima, Tatiani B Righeto, Germanna Lima Zanchin, Nilson Ivo Tonin Brandão-Neto, José Sandy, James Pereira, Humberto D'muniz Ferrari, Állan J. R. Gozzo, Fabio C. Smetana, Juliana H. C. Aparicio, Ricardo |
| dc.subject.other.pt_BR.fl_str_mv |
Elementos Estruturais de Proteínas |
| topic |
Elementos Estruturais de Proteínas Protein Phosphatase 2 Protein Structural Elements Mass Spectrometry Proteína Fosfatasa 2 Elementos Estructurales de las Proteínas Espectrometría de Masas Proteína Fosfatase 2 Espectrometria de Massas |
| dc.subject.en.pt_BR.fl_str_mv |
Protein Phosphatase 2 Protein Structural Elements Mass Spectrometry |
| dc.subject.es.pt_BR.fl_str_mv |
Proteína Fosfatasa 2 Elementos Estructurales de las Proteínas Espectrometría de Masas |
| dc.subject.decs.pt_BR.fl_str_mv |
Proteína Fosfatase 2 Espectrometria de Massas |
| description |
Institute 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. |
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2016 |
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2016 |
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2017-07-26T14:29:12Z |
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2017-07-26T14:29:12Z |
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SCORSATO, 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. |
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10.1038/srep30813 |
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SCORSATO, 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. 2045-2322 10.1038/srep30813 |
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