Protein folding apolar amino acid residues

The folding of a protein in an aqueous milieu follows a clear-cut biochemical logic. Apolar residues isolate themselves from water by burrowing into the apolar phase that they autocreate. The apolar core of the protein groups most of the apolar amino acid residues into the center of a roughly spherical structure from which water molecules are totally excluded (Fig. 8.3). 

The van der Waals model of monomeric insulin (1) once again shows the wedge-shaped tertiary structure formed by the two chains together. In the second model (3, bottom), the side chains of polar amino acids are shown in blue, while apolar residues are yellow or pink. This model emphasizes the importance of the hydrophobic effect for protein folding (see p. 74). In insulin as well, most hydrophobic side chains are located on the inside of the molecule, while the hydrophilic residues are located on the surface. Apparently in contradiction to this rule, several apolar side chains (pink) are found on the surface. However, all of these residues are involved in hydrophobic interactions that stabilize the dimeric and hexameric forms of insulin. 

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