Opening Image: Surface model of cryptogein complexed to cholesterol.

The very property that makes cholesterol useful in cell membranes, namely, its absolute insolubility in water, requires water-soluble proteins like crytogenin which can bind cholesterol or other sterols and transport them to and from different cells. Cryptogein is such protein. It is secreted by certain fungi and acts as a catalyst to shuttle plant sterols from the membrane of infected plant cells to the pathogen, allowing it to grow.

Cholesterol (CPK model) was substituted for plant sterol in the crystal structure. It binds in the large inner hydrophobic cavity. Hydrophobic sidechains of the protein in van der Waals contact with cholesterol are colored green. Hide the cholesterol molecule to examine the central cavity.

The hydrophobic effect is the tendency for nonpolar molecules to associate in solution. The concept arose from a well known fact: oil and water do not mix. The reason is that water is more stable when the oil is not dissolved in it than when the oil is. Water expels oil and other solutes that neither are ions nor have significant numbers of hydrogen bond donors and acceptors. The same effect causes nonpolar side chains of a protein to gather together during folding to form a hydrophobic core which stabilizes the protein. This process is not unique to proteins; nature makes use of the hydrophobic effect in the formation of many other biological structures, including DNA and lipid membranes.

The hydrophobic effect follows from water's unusually high cohesion, which in turn follows from the highly directional character of the hydrogen bond and water's ability to form a three-dimensional network of hydrogen bonds. To understand the importance of the hydrogen bond in the hydrophobic effect we begin with the simplest example of the hydrophobic effect, the poor solubility of methane in water. This will provide us with the background for other, more complex, and certainly much more important, phenomena in which the hydrophobic effect plays an important role. We'll also explore the hydration of uracil and thymine, two bases found in nucleic acids. Finally, there's a simple example of the role of the hydrophobic effect in molecular recognition.