The term secondary structure refers to the interaction of the hydrogen bond donor and acceptor residues of the repeating peptide unit. The two most important secondary structures of proteins, the alpha helix and the beta sheet, were predicted by the American chemist Linus Pauling in the early 1950s. Pauling and his associates recognized that folding of peptide chains, among other criteria, should preserve the bond angles and planar configuration of the peptide bond, as well as keep atoms from coming together so closely that they repelled each other through van der Waal's interactions. Finally, Pauling predicted that hydrogen bonds must be able to stabilize the folding of the peptide backbone. Two secondary structures, the alpha helix and the beta pleated sheet, fulfill these criteria well (see Figure ). Pauling was correct in his prediction. Most defined secondary structures found in proteins are one or the other type.
Figure 1
Alpha helix. The alpha helix involves regularly spaced H‐bonds between residues along a chain. The amide hydrogen and the carbonyl oxygen of a peptide bond are H‐bond donors and acceptors respectively:
The alpha helix is right‐handed when the chain is followed from the amino to the carboxyl direction. (The helical nomenclature is easily visualized by pointing the thumb of the right hand upwards—this is the amino to carboxyl direction of the helix. The helix then turns in the same direction as the fingers of the right hand curve.) As the helix turns, the carbonyl oxygens of the peptide bond point upwards toward the downward‐facing amide protons, making the hydrogen bond. The R groups of the amino acids point outwards from the helix.
Helices are characterized by the number of residues per turn. In the alpha helix, there is not an integral number of amino acid residues per turn of the helix. There are 3.6 residues per turn in the alpha helix; in other words, the helix will repeat itself every 36 residues, with ten turns of the helix in that interval.
Beta sheet. The beta sheet involves H‐bonding between backbone residues in adjacent chains. In the beta sheet, a single chain forms H‐bonds with its neighboring chains, with the donor (amide) and acceptor (carbonyl) atoms pointing sideways rather than along the chain, as in the alpha helix. Beta sheets can be either parallel, where the chains point in the same direction when represented in the amino‐ to carboxyl‐ terminus, or antiparallel, where the amino‐ to carboxyl‐ directions of the adjacent chains point in the same direction. (See Figure 2 .)
Figure 2
Different amino acids favor the formation of alpha helices, beta pleated sheets, or loops. The primary sequences and secondary structures are known for over 1,000 different proteins. Correlation of these sequences and structures revealed that some amino acids are found more often in alpha helices, beta sheets, or neither. Helix formers include alanine, cysteine, leucine, methionine, glutamic acid, glutamine, histidine, and lysine. Beta formers include valine, isoleucine, phenylalanine, tyrosine, tryptophan, and threonine. Serine, glycine, aspartic acid, asparagine, and proline are found most often in turns.
No relationship is apparent between the chemical nature of the amino acid side chain and the existence of amino acid in one structure or another. For example, Glu and Asp are closely related chemically (and can often be interchanged without affecting a protein's activity), yet the former is likely to be found in helices and the latter in turns. Rationalizing the fact that Gly and Pro are found in turns is somewhat easier. Glycine has only a single hydrogen atom for its side chain. Because of this, a glycine peptide bond is more flexible than those of the other amino acids. This flexibility allows glycine to form turns between secondary structural elements. Conversely, proline, because it contains a secondary amino group, forms rigid peptide bonds that cannot be accommodated in either alpha or beta helices.
The large‐scale characteristics of proteins are consistent with their secondary structures. Proteins can be either fibrous (derived from fibers) or globular (meaning, like a globe). Fibrous proteins are usually important in forming biological structures. For example, collagen forms part of the matrix upon which cells are arranged in animal tissues. The fibrous protein keratin forms structures such as hair and fingernails. The structures of keratin illustrate the importance of secondary structure in giving proteins their overall properties.
Alpha keratin is found in sheep wool. The springy nature of wool is based on its composition of alpha helices that are coiled around and cross‐linked to each other through cystine residues. Chemical reduction of the cystine in keratin to form cysteines breaks the cross‐links. Subsequent oxidation of the cysteines allows new cross‐links to form. This simple chemical reaction sequence is used in beauty shops and home permanent products to restructure the curl of human hair—the reducing agent accounts for the characteristic odor of these products. Beta keratin is found in bird feathers and human fingernails. The more brittle, flat structure of these body parts is determined by beta keratin being composed of beta sheets almost exclusively.
Globular proteins, such as most enzymes, usually consist of a combination of the two secondary structures—with important exceptions. For example, hemoglobin is almost entirely alpha‐helical, and antibodies are composed almost entirely of beta structures. The secondary structures of proteins are often depicted in ribbon diagrams, where the helices and beta sheets of a protein are shown by corkscrews and arrows respectively, as shown in Figure 3 .
Figure 3