increase the conformational stability of globular proteins (Section 7.2.2)
generally decrease their solubility; compare Figures 7.8a and 7.12b.
However, the agreement is not perfect. The greater effect of sodium sulfate
compared to the ammonium salt, for example, does not agree with their
position in the Hofmeister series.ðNH 4 Þ 2 SO 4 is often used for salting out
proteins, as it is very effective and also very soluble, so that high
concentrations can be reached. Since the salt enhances conformational
stability, the precipitation of the protein is reversible: diluting the system
with water or dialyzing the salt away causes the protein to dissolve again in
an undenatured state. Ions at the end of the Hofmeister series, such as
chlorides, do not cause salting out of hydrophilic proteins (Figure 7.13b).
In accordance with this, H 2 SO 4 is generally much more effective than
HCl in realizing isoelectric precipitation of proteins. Proteins vary greatly in
their susceptibility to become salted out, as shown in Figure 7.13c.
Hydrophobic proteins can even be salted out by high concentrations
of NaCl.
Other Aspects. Severalnonionic solutesalso affect solubility. Most
sugars increase the surface tension of water somewhat, and tend to reduce
protein solubility. Alcohols strongly decrease surface tension and tend to
increase markedly the solubility of hydrophobic proteins. On the other
hand, they decrease the dielectric constant, thereby enhancing electrostatic
bonding. This implies that alcohols tend to decrease solubility at higher
concentrations, especially of hydrophilic proteins. The same holds for most
FIGURE7.13 Salting out: solubility of proteins (csat) as a function of ionic strength
(I). (a and b) Hemoglobin; salts indicated. (c) fibrinogen (F), hemoglobin (H), serum
albumin (S), and myoglobin (M); salt (NH 4 ) 2 SO 4.