How does pH change protein structure?

The interactions between the side chains of the amino acids determine the shape of a protein.

Four types of attractive interactions determine the shape and stability of a protein. The two that pH changes affect are salt bridges (a) and hydrogen bonding (b).

Salt Bridges

Salt bridges are ionic bonds between positively and negatively charged side chains of amino acids. An example is the attraction between a #"-COO"^"-"# ion of lysine and an #"-NH"_3^"+"# ion of aspartic acid.

Increasing the pH by adding a base converts the #"-NH"_3^"+"# ion to a neutral #"-NH"_2# group.

Decreasing the pH by adding an acid converts the #"–COO"^"-" # ion to a neutral #"-COOH"# group.

In each case the ionic attraction disappears, and the protein shape unfolds.

Hydrogen Bonding

Various amino acid side chains can hydrogen bond to each other. Examples are:

• Two alcohols: Ser, Thr, and Tyr.
• Alcohol and amine: Ser and Lys
• Alcohol and amide: Ser and Asn
• Alcohol and acid: Asp and Tyr
• Two acids: Asp and Glu

Changing the pH disrupts the hydrogen bonds, and this changes the shape of the protein.