Conformational effects in protein electrospray-ionization mass spectrometry

Electrospray-ionization mass spectrometry (ESI-MS) is a key tool of structural biology, complementing the information delivered by conventional biochemical and biophysical methods. Yet, the mechanism behind the conformational effects in protein ESI-MS is an object of debate. Two parameters - solvent-accessible surface area (As) and apparent gas-phase basicity (GBapp) - are thought to play a role in controlling the extent of protein ionization during ESI-MS experiments. This review focuses on recent experimental and theoretical investigations concerning the influence of these parameters on ESI-MS results and the structural information that can be derived. The available evidence supports a unified model for the ionization mechanism of folded and unfolded proteins. These data indicate that charge-state distribution (CSD) analysis can provide valuable structural information on normally folded, as well as disordered structures.