Secondary Structure (General)

The term "secondary structure" refers to local folding of the backbone of a linear polymer to form a regular, repeating structure. For a polypeptide, the secondary structure is determined by the amino acid sequence (i.e., the primary structure) and the solvent environment in which it is located.

The sequence of amino acids dictates certain geometric constraints for the polypeptide. These constraints include maximum lengths between covalent bonds, limiting angles in which bonds can be bent, and van der Waals radii, which limit how tightly structures can be packed. These factors, mixed with forces that help preferentially stabilize structures, such as hydrogen bonds, ionic attractions/repulsions, hydrophobic interactions, and others, ultimately determine the shape that a peptide has over a short distance. The structure resulting from all these interactions is called the secondary structure of the protein.

Secondary structure must not be confused with the overall shape of a polypeptide. The overall shape of a polypeptide arises from the different regions of secondary structure folding upon each other and is called the tertiary structure if it involves only the same peptide or the quaternary structure if it involves two or more separate peptides. For example, the complete structure of myoglobin in Figure 6.1 arises from primary structure (the sequence of amino acids shown as numbers), the secondary structure (the 3D scheme by which the individual amino acids are arranged with respect to each other), and the tertiary structure (the way in which the secondary structures are folded together to make the globular molecule).

Amino acids come in many shapes and sizes, and can have a range of charges at physiological pH (Figure 5.3). Despite their many differences, there is enough similarity between certain groups of these amino acids that they form the same general secondary structure, if located close together in the polypeptide chain.

An interesting aspect of secondary structure is that, despite the different sizes, shapes, and charges of the amino acids, regular repeating structural motifs are common in globular proteins. For example, the -helix and the -sheet (Figure 6.3) are common secondary structures found in many proteins and were predicted theoretically by Linus Pauling. To do this, he applied his knowledge of the structure of the amino acids and his understanding of covalent bonding (i.e., bond lengths, bond angles, and van der Waals radii).

Besides the -helix and the -sheet, other secondary structures include the 3 10 helix (observed in some polypeptides) and the helix (Figure 6.4), which is theoretically possible, but has never been found in a protein. Table 6.1 lists five actual or theoretical secondary structures in polypeptides. Note that parallel/antiparallel indicates chain structures running in the same or opposite orientations, respectively.

There is considerably more potential for a polypeptide to assume many different structures than it actually does. Theoretically, every single bond in a polypeptide could freely rotate (Figure 6.2), but there are stabilizing forces (as well as repulsive forces) that help to significantly limit the number of possible configurations in a polypeptide.

See also: Secondary Structures (Specific examples), Prediction of Secondary and Tertiary Protein Structure, -Helix, -Sheet