Intrinsically disordered proteins (IDPs) exert key biological functions but tend to escape identification and characterization due to their high structural dynamics and heterogeneity. The possibility to dissect conformational ensembles by electrospray-ionization mass spectrometry (ESI-MS) offers an attracting possibility to develop a signature for this class of proteins based on their peculiar ionization behavior. This review summarizes available data on charge-state distributions (CSDs) obtained for IDPs by non-denaturing ESI-MS, with reference to globular or chemically denatured proteins. The results illustrate the contributions that direct ESI-MS analysis can give to the identification of new putative IDPs and to their conformational investigation.
Keywords: IDP compaction; Sic1; charge-state distributions; charge-to-mass relation; intrinsically folded structural units; native mass spectrometry; protein folding; proteomics; solvent-accessible surface area; α-synuclein.