Intrinsically disordered proteins (IDPs) represent a family of proteins that lack secondary or tertiary structure. IDPs are hubs in interaction networks, , participate in liquid-liquid separation processes, and drive the formation of proteinaceous membrane-less organelles.. Their unfolded structure makes them particularly prone to post-translational modifications (PTMs) that play key functional modulatory roles. Areas covered: We discuss different analytical approaches to study phosphorylation of IDPs starting from methods for IDP enrichment (strong acid extractions and heat-based pre-fractionation), strategies to enrich and map phosphopeptides/proteins, and mass spectrometry-based tools to study the phosphorylation-dependent conformational alterations of IDPs (limited proteolysis, HDX, chemical cross-linking, covalent labeling, and ion mobility). Expert opinion: There is a growing interest in IDPs and their PTMs since they are involved in several diseases. The intrinsic disorder could be exploited to facilitate purification and synthetic production of IDPs taking full advantage of those structural mass-spectrometry-based methods that can be used to investigate IDPs and their phospho-dependent conformational alterations. The diffusion and implementation of mass spectrometers with ion mobility devices and electron transfer dissociation capabilities could be key-elements for increasing information on IDP biology.

Proteomic tools to study phosphorylation of intrinsically disordered proteins

Luca Secco;Guidalberto Manfioletti;Riccardo Sgarra
2023-01-01

Abstract

Intrinsically disordered proteins (IDPs) represent a family of proteins that lack secondary or tertiary structure. IDPs are hubs in interaction networks, , participate in liquid-liquid separation processes, and drive the formation of proteinaceous membrane-less organelles.. Their unfolded structure makes them particularly prone to post-translational modifications (PTMs) that play key functional modulatory roles. Areas covered: We discuss different analytical approaches to study phosphorylation of IDPs starting from methods for IDP enrichment (strong acid extractions and heat-based pre-fractionation), strategies to enrich and map phosphopeptides/proteins, and mass spectrometry-based tools to study the phosphorylation-dependent conformational alterations of IDPs (limited proteolysis, HDX, chemical cross-linking, covalent labeling, and ion mobility). Expert opinion: There is a growing interest in IDPs and their PTMs since they are involved in several diseases. The intrinsic disorder could be exploited to facilitate purification and synthetic production of IDPs taking full advantage of those structural mass-spectrometry-based methods that can be used to investigate IDPs and their phospho-dependent conformational alterations. The diffusion and implementation of mass spectrometers with ion mobility devices and electron transfer dissociation capabilities could be key-elements for increasing information on IDP biology.
2023
27-mag-2023
Pubblicato
https://www.tandfonline.com/doi/full/10.1080/14789450.2023.2217359
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/3056378
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