Protective Effects of Dimethyl Sulfoxide on Labile
Protein Interactions during Electrospray Ionization
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Abstract
Electrospray ionization mass spectrometry
is a valuable tool to
probe noncovalent interactions. However, the integrity of the interactions
in the gas-phase is heavily influenced by the ionization process.
Investigating oligomerization and ligand binding of transthyretin
(TTR) and the chaperone domain from prosurfactant protein C, we found
that dimethyl sulfoxide (DMSO) can improve the stability of the noncovalent
interactions during the electrospray process, both regarding ligand
binding and the protein quaternary structure. Low amounts of DMSO
can reduce in-source dissociation of native protein oligomers and
their interactions with hydrophobic ligands, even under destabilizing
conditions. We interpret the effects of DMSO as being derived from
its enrichment in the electrospray droplets during evaporation. Protection
of labile interactions can arise from the decrease in ion charges
to reduce the contributions from Coulomb repulsions, as well as from
the cooling effect of adduct dissociation. The protective effects
of DMSO on labile protein interactions are an important property given
its widespread use in protein analysis by electrospray ionization
mass spectrometry (ESI-MS)