How does protein precipitation work?

Protein precipitation results from changing the solubility of the protein in solution by the addition of various precipitants such as organic solvent, metal ion, acid, and salt. Precipitation by organic solvent or acid is most commonly used.


Organic solvent solvates the hydrophobic region on the protein surface and displaces water molecules. This causes an increase in electrostatic interactions, encourages attraction between charged molecules, and proteins aggregate as a result; this reduces their solubility, causing precipitation.

Acids form insoluble salts with proteins, causing precipitation.