Principles of Protein Structure - G. Schulz 1982

Mechanisms of polypeptide chain folding and association
Aggregates of globular proteins
Contact surfaces

The more extensive the contacts, the stronger the interaction. A detailed Analysis of Protein–protein contact surfaces was performed for the Proteins listed in Table 5.5. The data in this table indicate the presence of numerous Structure/103.html">Van der Waals contacts, as well as The formation of several Hydrogen Bonds and salt bridges. Obviously, as the number of contacts between subunits increases, the protein–protein interaction becomes stronger, as illustrated by the following four Examples.

In Hemoglobin, the z₁β₁ contact is the strongest. As seen from Table 5.5, in both oxy- and deoxyhemoglobin, the a₁β₁ (a₂β₂) contact is stronger than the a₁β₂ (a₂β₁) contact. It is known that the cooperative conformational change of hemoglobin upon oxygen saturation primarily involves a 13° Rotation of the a₁β₁ dimer relative to the a₂β₂ dimer. The a₁a₂ and β₁β₂ contacts are very weak (in a hemoglobin molecule with strict 222 symmetry, the a₁a₂ contact should be equivalent to the β₁β₂ contact). As noted above, this third type of contact in the 222 tetramer is not essential for holding the subunits together.

* The special position of Alcohol dehydrogenase is also reflected by the fact that its nucleotide-binding domain is located at the C-terminus of the polypeptide chain, whereas in the other three dehydrogenases this domain is at their N-terminus.

Class="center">Table 5.5 Protein–Protein Contacts

Contacts are often mediated by β-pleated sheets. In concanavalin A, one of the three contact types (I–IV) is also much weaker than the other two. The I–II contact, involving 14 hydrogen bonds, is particularly robust. In this case, a broad (six-stranded) β-structure crosses the twofold axis, resulting in a regular 12-stranded β-structure. The two strands linked by the twofold-axis-crossing Hydrogen bonds are antiparallel, meaning that this axis is perpendicular to the sheet plane. Such extensions of β-structures at protein–protein interfaces are common in subunit aggregates and Structural domains.

The contacts observed in crystals of concanavalin A, insulin, and a-chymotrypsin assist in determining The structure of dimers in solution.

In solution, tetrameric concanavalin A exists in equilibrium with dimers and monomers. Since the dimer exhibits physiological activity, its identification is of considerable interest. Given that among the Three types of dimers, the I–II dimer is likely the most stable (Table 5.5), it is most probable that this specific dimer exists in solution.

A similar issue arises in the case of insulin. In solution, the insulin hexamer is in equilibrium with dimers and monomers. Since the dimer appears to be important for hormone-receptor binding, it needs to be identified. Judging by the values given in Table 5.5, the strengths of the two possible dimers should not differ significantly. However, the OP dimer forms an antiparallel β-structure In addition to a slightly stronger contact. Therefore, it is reasonable to conclude that this particular dimer is present in solution [259].

Crystalline a-chymotrypsin forms Two Types of contacts, A and B, associated with twofold axes of symmetry. Contact A is much stronger than contact B. In solution, at the pH of the crystals (pH 4), a-chymotrypsin forms dimers. The data presented in Table 5.5 strongly suggest that these dimers most likely belong to type A.