Binding Mechanisms of Intrinsically ...
Document type :
Article dans une revue scientifique
DOI :
Permalink :
Title :
Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment
Author(s) :
Mollica, Luca [Auteur]
Bessa, Luiza M. [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Hanoulle, Xavier [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Jensen, Malene Ringkjøbing [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Blackledge, Martin [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Schneider, Robert [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bessa, Luiza M. [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Hanoulle, Xavier [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Jensen, Malene Ringkjøbing [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Blackledge, Martin [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Schneider, Robert [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Journal title :
Frontiers in Molecular Biosciences
Volume number :
3
Publication date :
2016-09-09
ISSN :
2296-889X
English keyword(s) :
intrinsically disordered proteins
protein-protein interactions
nuclear magnetic resonance
kinetics
molecular dynamics simulations
protein-protein interactions
nuclear magnetic resonance
kinetics
molecular dynamics simulations
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure ...
Show more >In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed, e.g., in the “fly-casting” hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit), are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context.Show less >
Show more >In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed, e.g., in the “fly-casting” hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit), are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
RMN et interactions moléculaires
Submission date :
2020-02-12T15:45:02Z
2021-07-13T14:20:06Z
2021-07-13T14:20:06Z
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