Quaternary structure arises when multiple protein subunits interact with each other. This organization may be homotypic or heterotypic. Homotypic quaternary structure occurs when identical or nearly identical polypeptide chains interact. Heterotypic quaternary structure occurs when subunits of very different structures interact. A multi-subunit protein like hemoglobin, therefore, has the four levels of structure shown in Figure 6.29.

Interactions between polypeptide subunits that stabilize the multisubunit structure are the same as the ones stabilizing tertiary structure - salt bridges, hydrogen bonds, van der Waals forces, hydrophobic interactions and (occasionally) disulfide bonds.

Homotypic - The individual subunits are usually asymmetric. If they are identical, however, their pattern of arrangement can give rise to an overall symmetry in the complex. Several types of symmetry, ranging from simple to complex, are shown in Figure 6.30. One of these types of symmetry, helical symmetry, is shown in more detail in Figure 6.31.

Two-fold symmetries, such as shown in C2 symmetry (Figure 6.30b), are said to be isologous if two identical interactions occur between the subunits and heterologous if two different interactions occur. Additional isologous interactions can give rise to higher levels of symmetry, such as the D2 dihedral shown in Figure 6.30e.

Dimers (two subunits interacting) are the most common of all quaternary structures. Typically, they have isologous interactions, but Figure 6.31 illustrates how heterologous interactions can lead to a dimer without symmetry.

Heterotypic - Associations between differerent proteins are very common in cells and are stabilized by the same forces as homotypic interactions. For example BPTI forms a tight, specific complex with the enzyme trypsin that inhibits the ability of trypsin to function in the pancreas.