Research ExplorerPublicationsPharmacological inactivation of the prion protein by targeti...

Pharmacological inactivation of the prion protein by targeting a folding intermediate

Standard

Pharmacological inactivation of the prion protein by targeting a folding intermediate. / Spagnolli, Giovanni; Massignan, Tania; Astolfi, Andrea; Biggi, Silvia; Rigoli, Marta; Brunelli, Paolo; Libergoli, Michela; Ianeselli, Alan; Orioli, Simone; Boldrini, Alberto; Terruzzi, Luca; Bonaldo, Valerio; Maietta, Giulia; Lorenzo, Nuria L; Fernandez, Leticia C; Codeseira, Yaiza B; Tosatto, Laura; Linsenmeier, Luise; Vignoli, Beatrice; Petris, Gianluca; Gasparotto, Dino; Pennuto, Maria; Guella, Graziano; Canossa, Marco; Altmeppen, Hermann C; Lolli, Graziano; Biressi, Stefano; Pastor, Manuel M; Requena, Jesús R; Mancini, Ines; Barreca, Maria L; Faccioli, Pietro; Biasini, Emiliano.

In: COMMUN BIOL, Vol. 4, No. 1, 62, 12.01.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Spagnolli, G, Massignan, T, Astolfi, A, Biggi, S, Rigoli, M, Brunelli, P, Libergoli, M, Ianeselli, A, Orioli, S, Boldrini, A, Terruzzi, L, Bonaldo, V, Maietta, G, Lorenzo, NL, Fernandez, LC, Codeseira, YB, Tosatto, L, Linsenmeier, L, Vignoli, B, Petris, G, Gasparotto, D, Pennuto, M, Guella, G, Canossa, M, Altmeppen, HC, Lolli, G, Biressi, S, Pastor, MM, Requena, JR, Mancini, I, Barreca, ML, Faccioli, P & Biasini, E 2021, 'Pharmacological inactivation of the prion protein by targeting a folding intermediate', COMMUN BIOL, vol. 4, no. 1, 62. https://doi.org/10.1038/s42003-020-01585-x

APA

Spagnolli, G., Massignan, T., Astolfi, A., Biggi, S., Rigoli, M., Brunelli, P., Libergoli, M., Ianeselli, A., Orioli, S., Boldrini, A., Terruzzi, L., Bonaldo, V., Maietta, G., Lorenzo, N. L., Fernandez, L. C., Codeseira, Y. B., Tosatto, L., Linsenmeier, L., Vignoli, B., ... Biasini, E. (2021). Pharmacological inactivation of the prion protein by targeting a folding intermediate. COMMUN BIOL, 4(1), [62]. https://doi.org/10.1038/s42003-020-01585-x

Vancouver

Spagnolli G, Massignan T, Astolfi A, Biggi S, Rigoli M, Brunelli P et al. Pharmacological inactivation of the prion protein by targeting a folding intermediate. COMMUN BIOL. 2021 Jan 12;4(1). 62. https://doi.org/10.1038/s42003-020-01585-x

Bibtex

@article{f99f5ab007fe4a29b852068dd05e2639,
title = "Pharmacological inactivation of the prion protein by targeting a folding intermediate",
abstract = "Recent 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.",
author = "Giovanni Spagnolli and Tania Massignan and Andrea Astolfi and Silvia Biggi and Marta Rigoli and Paolo Brunelli and Michela Libergoli and Alan Ianeselli and Simone Orioli and Alberto Boldrini and Luca Terruzzi and Valerio Bonaldo and Giulia Maietta and Lorenzo, {Nuria L} and Fernandez, {Leticia C} and Codeseira, {Yaiza B} and Laura Tosatto and Luise Linsenmeier and Beatrice Vignoli and Gianluca Petris and Dino Gasparotto and Maria Pennuto and Graziano Guella and Marco Canossa and Altmeppen, {Hermann C} and Graziano Lolli and Stefano Biressi and Pastor, {Manuel M} and Requena, {Jes{\'u}s R} and Ines Mancini and Barreca, {Maria L} and Pietro Faccioli and Emiliano Biasini",
year = "2021",
month = jan,
day = "12",
doi = "10.1038/s42003-020-01585-x",
language = "English",
volume = "4",
journal = "COMMUN BIOL",
issn = "2399-3642",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Pharmacological inactivation of the prion protein by targeting a folding intermediate

AU - Spagnolli, Giovanni

AU - Massignan, Tania

AU - Astolfi, Andrea

AU - Biggi, Silvia

AU - Rigoli, Marta

AU - Brunelli, Paolo

AU - Libergoli, Michela

AU - Ianeselli, Alan

AU - Orioli, Simone

AU - Boldrini, Alberto

AU - Terruzzi, Luca

AU - Bonaldo, Valerio

AU - Maietta, Giulia

AU - Lorenzo, Nuria L

AU - Fernandez, Leticia C

AU - Codeseira, Yaiza B

AU - Tosatto, Laura

AU - Linsenmeier, Luise

AU - Vignoli, Beatrice

AU - Petris, Gianluca

AU - Gasparotto, Dino

AU - Pennuto, Maria

AU - Guella, Graziano

AU - Canossa, Marco

AU - Altmeppen, Hermann C

AU - Lolli, Graziano

AU - Biressi, Stefano

AU - Pastor, Manuel M

AU - Requena, Jesús R

AU - Mancini, Ines

AU - Barreca, Maria L

AU - Faccioli, Pietro

AU - Biasini, Emiliano

PY - 2021/1/12

Y1 - 2021/1/12

N2 - Recent 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.

AB - Recent 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.

U2 - 10.1038/s42003-020-01585-x

DO - 10.1038/s42003-020-01585-x

M3 - SCORING: Journal article

C2 - 33437023

VL - 4

JO - COMMUN BIOL

JF - COMMUN BIOL

SN - 2399-3642

IS - 1

M1 - 62

ER -