Elements of Protein Structure

Protein Structure Generalizations

The one unequivocal statement we can make about protein folding is that the sum of the energies for a properly folded protein must be favorable (relative to the unfolded) We know this because proteins fold!

The same statement put in terms of energy... The total energy for the folded protein must be lower than that for the unfolded protein. Nature is lazy - things tend to run downhill.

This is true for the sum over all of the interactions; including the ionic, the polar, the H-bonds, the Van Der Waal's interactions and the hydrophobic effect. This does NOT mean that ALL of the interactions are favorable... Indeed with the thousands of interactions in a single molecule it is difficult to conceive of a situation where they could be all favorable!! but rather a sort of optimal arrangement.

There are a few generalizations that can be pointed out.

For those proteins that are soluble in water.

First there are VERY few ionic interactions buried inside a protein structure. The vast majority of these are on the surface of a protein or at regions on the surface that interact with other proteins and molecules. The reason for this is two fold. Ions interact very favorably with water molecules; and there are very few water molecules found in the interior of proteins. So the ionic amino acids tend to be found in regions where water is present.

Second. The hydrophobic amino acids are found mostly in the interior of the protein because this is where they can hide from water. It turns out that the hydrophobic effect is probably the primary force into inducing a protein to fold at all.

Third. The hydrophobic effect lacks specificity and directionality. So while the hydrophobic effect may induce the polypeptide to start folding it is the polar and H-bond interactions (which indeed have direction and some specificity) that give the protein its specific shape!


The initial picture is a ribbon representation of Factor VIIa. Helices are green; Sheets are purple and the randon coil regions are colored red.


Some proteins are embedded in the cell membrane.

So far only water soluble proteins have been addressed. These are proteins that would be found in in the cell's cytosol or in other fluids such as blood serum. There are many proteins that are not found here but in the cell membranes, the mitochondrial membranes or in platlets of blood. For these proteins, the same set of interactions apply. The primary difference is that instead of being water soluble, these proteins (or parts) are lipid (oil) soluble.

Of course the solvent effects are the opposite of that found in water. For the regions of a protein that is in contact with the center of the membrane, the generalizations discussed above can be reversed. In the next two pages we will see what the structure of a membrane is and how protein structure changes to be soluble in the membrane.