Session 5 -- Page 1
July 10, 2000

OVERVIEW

We're going to develop the following themes in this session.

• Proteins generally have convoluted and tangled three dimensional structures.
• Their labyrinthine organization allows proteins to perform a wide variety of functions.
• An important function -- probably the most important function -- that proteins carry out is to act as enzymes: large molecules that have the ability to speed up specific chemical reactions.

The complexity of protein structures
John Kendrew, back in 1958, was the first person to piece together the three dimensional structure of a protein. The molecule that he studied was whale myoglobin, a protein involved in oxygen transport in muscle tissue. Using a technique called X-ray crystallography, and after a monumental effort in his laboratory at Cambridge University in England, he was able to deduce the three dimensional shape of myoglobin in all its byzantine complexity. When the final results came in, he seemed rather disappointed.

"Perhaps the most remarkable features of the molecule are its 
complexity and its lack of symmetry." 

(from "Introduction to Protein Structure", by Carl Branden and John Tooze, Garland Publishing, Inc., NY and London, 1991).

A picture of myoglobin, one that emphasizes its complexity, is shown below. You may manipulate this structure in various ways in order to try to make more sense of it.

The next molecule whose structure was deciphered, the related protein hemoglobin, was equally homely. The fact is that almost all proteins are complex, irregular molecules. When they are compared with DNA, whose structure is both simple and symmetrical, they appear downright ugly. The structure of DNA had been worked out almost five years earlier by Watson and Crick (We're going to talk more about the structure of DNA in a later session).

Linus Pauling
But despite the complexity of myoglobin, hemoglobin, and several hundred other proteins whose structure has been solved, many people have been able to recognize some regularities amidst this apparent chaos. One of the first was the late Linus Pauling, of vitamin C fame, who earned the first of two Nobel Prizes for his insights (the second Nobel was for peace). Pauling, working with Robert Corey in the early 1950's, predicted that proteins would carry certain regular structural features. This was years before anyone had an idea of what proteins really looked like. Corey and Pauling had carefully studied the structure of amino acids and very small peptides and built accurate models of these molecules. Then they played with the models, trying to make them fit together according to certain chemical rules.

Alpha helix
Pauling and Corey -- taking into account these basic principles -- tried to devise a structure for the peptide chain in which the maximum number of hydrogen bonds could be formed. They found two such shapes. One looked like a spring. This helical shape turned out to be present in myoglobin, the first protein whose structure was solved, and which is pictured above.

Notice (see the figure above) that if one fashions the peptide chain into a spring-shaped structure, and if the width of the spring is just right, the oxygen from one peptide bond and the nitrogen/hydrogen from one three units away come to lie very close to one another. This allows for the formation of a hydrogen bond, and for the regular formation of hydrogen bonds as long as the chain forms such a structure. Pauling and Corey called this spring-shaped form the alpha helix.

Beta sheet
Pauling and Corey also found that many hydrogen bonds would form if two parts of a peptide chain would pair up parallel with one another as shown in the figure at the right. They called this formation a beta structure, and it often referred to as a beta sheet.

Analysis of a large number of proteins has shown that a few are composed mostly of alpha helices (the proteins that make up most of your skin -- keratin -- is one of these, and so is myoglobin), and a few are composed almost exclusively of beta structures (silk fibroin, the protein that makes up silk is one of these). But most proteins -- especially the ones that I'll be discussing this summer -- are composed of sections that are in the form of helices, and other parts that are in the form of beta structures, and still other portions that are in much more complex shapes -- shapes that defy easy description.