Mostrar o rexistro simple do ítem

dc.contributor.authorSpagnolli, Giovanni
dc.contributor.authorMassignan, Tania
dc.contributor.authorAstolfi, Andrea
dc.contributor.authorBiggi, Silvia
dc.contributor.authorRigoli, Marta
dc.contributor.authorBrunelli, Paolo
dc.contributor.authorLibergoli, Michela
dc.contributor.authorIaneselli, Alan
dc.contributor.authorOrioli, Simone
dc.contributor.authorBoldrini, Alberto
dc.contributor.authorTerruzzi, Luca
dc.contributor.authorBonaldo, Valerio
dc.contributor.authorMaietta, Giulia
dc.contributor.authorLópez Lorenzo, Nuria
dc.contributor.authorFernández Flores, Leticia Camila
dc.contributor.authorBugallo Codeseira, Yaiza
dc.contributor.authorTosatto, Laura
dc.contributor.authorLinsenmeier, Luise
dc.contributor.authorVignoli, Beatrice
dc.contributor.authorPetris, Gianluca
dc.contributor.authorGasparotto, Dino
dc.contributor.authorPennuto, Maria
dc.contributor.authorGuella, Graziano
dc.contributor.authorCanossa, Marco
dc.contributor.authorAltmeppen, Hermann C.
dc.contributor.authorLolli, Graziano
dc.contributor.authorBiressi, Stefano
dc.contributor.authorMartín Pastor, Manuel
dc.contributor.authorRodríguez Requena, Jesús
dc.contributor.authorMancini, Ines
dc.contributor.authorBarreca, Maria L.
dc.contributor.authorFaccioli, Pietro
dc.contributor.authorBiasini, Emiliano
dc.date.accessioned2021-02-22T11:47:04Z
dc.date.available2021-02-22T11:47:04Z
dc.date.issued2021
dc.identifier.citationCommunications Biology volume 4, Article number: 62 (2021)
dc.identifier.urihttp://hdl.handle.net/10347/24542
dc.description.abstractRecent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression
dc.description.sponsorshipL.To. is supported by Fondazione Caritro (Bando Post Doc 2017) and Kennedy’s Disease Association (Research Grant 2018). Research of HCA was supported by the CJD Foundation, Inc. and the Alzheimer Forschung Initiative e.V. (AFI). J.R.R. was funded by a grant (BFU2017-86692-P) from the Spanish Ministry of Economy and Competitiveness, partially funded by FEDER funds. The work was also supported by grants from Fondazione Telethon and Provincia Autonoma di Trento to S.B. (TCP13007), from Fondazione Telethon to E.B. (TCP14009), and by a fellowship from Fondazione Telethon to G.S. S.B. and E.B. are Assistant Telethon Scientists at the Dulbecco Telethon Institute
dc.language.isoeng
dc.publisherSpringer Nature
dc.rights© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.rightsAtribución 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectComputational biophysics
dc.subjectPrions
dc.subjectVirtual screening
dc.titlePharmacological inactivation of the prion protein by targeting a folding intermediate
dc.typejournal article
dc.identifier.doi10.1038/s42003-020-01585-x
dc.relation.publisherversionhttps://doi.org/10.1038/s42003-020-01585-x
dc.type.hasVersionVoR
dc.identifier.essn2399-3642
dc.rights.accessRightsopen access
dc.contributor.affiliationUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
dc.description.peerreviewedSI


Ficheiros no ítem

application/pdf
Nome: 2021_cb_spagnolli_pharmacological .pdf
Tamaño: 3.901 Mb
Formato: PDF


Thumbnail

Este ítem aparece na(s) seguinte(s) colección(s)

Mostrar o rexistro simple do ítem

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
A licenza do ítem descríbese como
 © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/





Recolectores:Enlaces de interese:
Universidade de Santiago de Compostela | Teléfonos: +34 881 811 000 e +34 982 820 000 | Contacto | Suxestións