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Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls

Many proteins lack a well-defined three-dimensional structure in isolation. These proteins, typically denoted as intrinsically disordered proteins (IDPs), may display a characteristic disorder-to-order transition when binding their physiological partner(s). From an experimental perspective, it is of...

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Autores principales: Malagrinò, Francesca, Visconti, Lorenzo, Pagano, Livia, Toto, Angelo, Troilo, Francesca, Gianni, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279032/
https://www.ncbi.nlm.nih.gov/pubmed/32429036
http://dx.doi.org/10.3390/ijms21103484
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author Malagrinò, Francesca
Visconti, Lorenzo
Pagano, Livia
Toto, Angelo
Troilo, Francesca
Gianni, Stefano
author_facet Malagrinò, Francesca
Visconti, Lorenzo
Pagano, Livia
Toto, Angelo
Troilo, Francesca
Gianni, Stefano
author_sort Malagrinò, Francesca
collection PubMed
description Many proteins lack a well-defined three-dimensional structure in isolation. These proteins, typically denoted as intrinsically disordered proteins (IDPs), may display a characteristic disorder-to-order transition when binding their physiological partner(s). From an experimental perspective, it is of great importance to establish the general grounds to understand how such folding processes may be explored. Here we discuss the caveats and the pitfalls arising when applying to IDPs one of the key techniques to characterize the folding of globular proteins, the Φ value analysis. This method is based on measurements of the free energy changes of transition and native states upon conservative, non-disrupting, mutations. On the basis of available data, we reinforce the validity of Φ value analysis in the study of IDPs and suggest future experiments to further validate this powerful experimental method.
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spelling pubmed-72790322020-06-15 Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls Malagrinò, Francesca Visconti, Lorenzo Pagano, Livia Toto, Angelo Troilo, Francesca Gianni, Stefano Int J Mol Sci Review Many proteins lack a well-defined three-dimensional structure in isolation. These proteins, typically denoted as intrinsically disordered proteins (IDPs), may display a characteristic disorder-to-order transition when binding their physiological partner(s). From an experimental perspective, it is of great importance to establish the general grounds to understand how such folding processes may be explored. Here we discuss the caveats and the pitfalls arising when applying to IDPs one of the key techniques to characterize the folding of globular proteins, the Φ value analysis. This method is based on measurements of the free energy changes of transition and native states upon conservative, non-disrupting, mutations. On the basis of available data, we reinforce the validity of Φ value analysis in the study of IDPs and suggest future experiments to further validate this powerful experimental method. MDPI 2020-05-15 /pmc/articles/PMC7279032/ /pubmed/32429036 http://dx.doi.org/10.3390/ijms21103484 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Malagrinò, Francesca
Visconti, Lorenzo
Pagano, Livia
Toto, Angelo
Troilo, Francesca
Gianni, Stefano
Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls
title Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls
title_full Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls
title_fullStr Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls
title_full_unstemmed Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls
title_short Understanding the Binding Induced Folding of Intrinsically Disordered Proteins by Protein Engineering: Caveats and Pitfalls
title_sort understanding the binding induced folding of intrinsically disordered proteins by protein engineering: caveats and pitfalls
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279032/
https://www.ncbi.nlm.nih.gov/pubmed/32429036
http://dx.doi.org/10.3390/ijms21103484
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