In this module:

Protein Folding

How do proteins "know" how to fold into the complicated three-dimensional structures you have seen here? This is a very active area of research in biochemistry right now. The first hint came from the work of Christian Anfinsen on the protein ribonuclease (right), which breaks down RNA molecules (See the DNA 2 module for a discussion of RNA). Anfinsen discovered that when ribonuclease is treated with high concentrations of certain chemicals that cause proteins to unfold and lose their tertiary and secondary structure in the test tube, it no longer broke down RNA. But if the chemicals were removed, the ribonuclease would spontaneously recover nearly all its RNA-hydrolyzing activity, in the complete absence of any other cellular components. Anfinsen concluded that the primary structure of a protein completely determines its three-dimensional structure at the secondary, tertiary, and quaternary levels.

Scientists are still trying to learn how the primary structure of a protein determines its other levels of structure. They have determined the primary forces that stabilize a protein's three-dimensional structure:

• Sequestration of hydrophobic amino acids away from water (in the interior of water-soluble proteins, for example)
• Maximizing van der Waals contacts in the interior of proteins (minimizing open space)
• Maximizing hydrogen bonds (in α helices or ß sheets, for example)
• Ion pairing between oppositely charged amino acids (Arg and Glu, for example)