title: Are Charge-State Distributions a Reliable Tool Describing Molecular Ensembles of Intrinsically Disordered Proteins by Native MS?
abstract: Native mass spectrometry (MS) has become a central tool of structural proteomics, but its applicability to the peculiar class of intrinsically disordered proteins (IDPs) is still object of debate. IDPs lack an ordered tridimensional structure and are characterized by high conformational plasticity. Since they represent valuable targets for cancer and neurodegeneration research, there is an urgent need of methodological advances for description of the conformational ensembles populated by these proteins in solution. However, structural rearrangements during electrospray-ionization (ESI) or after the transfer to the gas phase could affect data obtained by native ESI-MS. In particular, charge-state distributions (CSDs) are affected by protein conformation inside ESI droplets, while ion mobility (IM) reflects protein conformation in the gas phase. This review focuses on the available evidence relating IDP solution ensembles with CSDs, trying to summarize cases of apparent consistency or discrepancy. The protein-specificity of ionization patterns and their responses to ligands and buffer conditions suggests that CSDs are imprinted to protein structural features also in the case of IDPs. Nevertheless, it seems that these proteins are more easily affected by electrospray conditions, leading in some cases to rearrangements of the conformational ensembles. Graphical Abstract ᅟ.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Santambrogio
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy. rita.grandori@unimib.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
mesh_terms: D000818:Animals; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000737:chemistry; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D055672:Static Electricity; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D064267:Intrinsically Disordered Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53
keywords: Conformational effects; ESI mechanism; Intermediate regime; Protein structure; Structural disorder