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Origin of the conformation dependence of protein charge‐state distributions in electrospray ionization mass spectrometry
Author(s) -
Grandori Rita
Publication year - 2003
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.390
Subject(s) - chemistry , electrospray ionization , electrospray , chemical physics , ionization , ion , mass spectrometry , intramolecular force , charge (physics) , mass spectrum , crystallography , computational chemistry , analytical chemistry (journal) , stereochemistry , chromatography , organic chemistry , quantum mechanics , physics
The influence of tertiary structure on the electrospray ionization mass spectra of proteins is a well known and broadly exploited phenomenon. However, the underlying mechanism is not well understood. This paper discusses the bases and the implications of the two current hypotheses (solvent accessibility and Coulombic repulsions), pointing out the remaining open questions. Evidence reported here supports a third hypothesis, i.e. that intramolecular interactions in folded proteins play a key role in determining the observed charge‐state distributions. It is proposed that native protein structures stabilize to a large extent pre‐existing charges of the opposite polarity to the net charge of the ion, preventing their neutralization during the electrospray process. Thus, the higher charge states of unfolded conformations, relative to the folded structure, would not derive from a more extensive ionization of the former, but rather from a higher content of neutralizing charges in the latter. This interpretation allows several other problematic observations to be explained, including the different shapes of the spectra of folded and unfolded proteins, the discrepancies between observed and predicted gas‐phase reactivity of protein ions and the apparent inconsistency of positive‐ and negative‐ion mode results. Copyright © 2003 John Wiley & Sons, Ltd.