Proteins are naturally occurring linear polymers of between fifty and two thousand monomer units called amino acids. Within proteins, the amino acids interact with each other to give four different levels of structure, from linear to complex.
Before discussing how the amino acids combine to give proteins, and the shorter oligopeptide chains, their linear and three-dimensional structures, it is important to first define amino acids. To date, twenty different amino acids have been discovered that function as the building blocks of proteins. Each amino acid subunit consists of a central alpha carbon atom that is chiral due to the four different side groups to which it is bonded. The first bond formed on the central alpha carbon is a single bond to a hydrogen atom. The second bond formed on the central alpha carbon is a single bond to an amine functional group (-NH2). The third bond formed on the central alpha carbon is a single bond to a carboxylic acid functional group (-COOH). The final bond formed on the central alpha carbon is a single bond to one of twenty distinct functional side groups, called R groups. This R group is the variable that defines each amino acid, and it consists of one or more carbons with or without other functional groups attached. Due to these side groups, amino acids are typically found in the ionized form at physiological pH, 7.4, as zwitterions, in which the carboxylic acid donates a hydrogen atom while the amine group accepts a hydrogen atom. Thus, the zwitterions are dipolar yet have an overall neutral charge. In addition, the chiral nature of the central carbon allows for both the L and D isomers of each amino acid to be formed, although only the L isomers are found in nature.
The primary structure of a protein is simply its linear sequence of amino acids. A protein maintains its particular sequence of amino acid order due to the peptide bonds formed between the amine group of one amino acid and the carboxylic acid group of a second amino acid. The precise order of the amino acids in a protein is determined by genetic information carried on the cell’s DNA and translated and transcribed by the cell’s RNA. Also called amide bonds, it is the dehydration reaction peptide bonds that order the amino acid subunits in sequences that determine the biological function of a given protein or peptide. Because they are formed by a dehydration reaction, peptide bonds may be broken by hydrolysis.
The secondary structure of a protein refers to a localized structure that is regular and repeated, and that forms when amino acids form hydrogen bonds either within the same chain or between multiple polypeptides. It is only the hydrogens on the polypeptide chains that interact to form the local patterns of secondary structures, not eh R groups. Alpha helices, the most common type of secondary structure seen in proteins, are coiled structures that form when an N-H group forms a hydrogen bond with a C=O group of the same polypeptide, leaving the side groups of the amino acids on the outside of the helix. Naturally occurring in only a right-handed coil, alpha helices look like corkscrews and are stabilized by the hydrogen bonds that are typically between individual amino acid residues that are four units apart within the polypeptide chain. Beta pleated sheets, or beta sheets, are ripple-like structures that form between polypeptides and place the side groups laying in opposite directions on the parallel polypeptide chains. In these zig-zag beta sheets, the chains themselves may run in either parallel or antiparallel directions, which means that they may both run from N-H to C=O or one may run from N-H to C=O while the other chain runs from C=O to N-H. A third type of secondary structure is the triple helix. A triple helix is formed when three polypeptide chains are braided together, and are typically found as structural proteins where strength is required. In addition to these three regular and repeating structures, there are also beta turns and omega loops within polypeptides that are classified as secondary structures. While turns and loops typically do not repeat as regularly as helices and sheets, they are structurally important foundations for the tertiary structure of a protein and are typically well-defined and rigid structures.
The tertiary structures of proteins refer to the three-dimensional shapes into which polypeptides naturally fold themselves, and they are given their stability by the attractions and repulsions of the side groups within a polypeptide. Complex and typically devoid of symmetry, tertiary structures are stabilized by any one or combinations of the following five interactions. Hydrophobic interactions occur between two nonpolar side groups and allow for the formation of a hydrophobic center within the interior of the protein molecule. Hydrophilic interactions occur between the aqueous environment of the protein and the polar side groups and allow for the polar side groups to be arranged on the surface of the protein to allow for interaction between the protein and water. Salt bridges occur when ionic bonds are formed between acidic and basic side groups. Hydrogen bonds occur between the hydrogen atoms of separate amino acid residues. Disulfide bonds occur between the –SH groups of cysteines in a polypeptide chain, creating covalent bonds. Two tertiary structures that proteins may fold themselves into are globular proteins and fibrous proteins. Globular proteins are spherical in nature, with hydrophobic interiors and hydrophilic surfaces, that carry out biological processes such as synthesis, transport, and metabolism within the cells and human body. Due to the arrangement of side groups in globular proteins, they are water soluble and chemically active. Fibrous proteins are similar to thin threads or longer cords and typically function in structural positions within cells and in the human body, as well as in certain contractile proteins of muscles. Due to the arrangement of side groups in fibrous proteins, the extended strands are insoluble in water and are typically very stable structures.
The final level of protein structure, quaternary structure, is a larger aggregate that is not evidenced in all proteins. Quaternary protein structure occurs when two or more polypeptide subunits are organized in a particular arrangement to form a biologically active protein. The closely associated subunits in quaternary structures are held together by the same side group interactions found in tertiary structures, and the individual subunits may be identical or there may be different subunits.
|Level||Definition||Bonds or Interactions||Examples|
|Primary||Linear sequence of amino acids||Peptide bonds between individual amino acids|
|Secondary||Localized structures that are regular and repeating||Hydrogen bonds within or between polypeptide chains||Alpha helix; beta sheet; triple helix; beta turn; omega loop|
|Tertiary||Three-dimensional structure that is typically devoid of symmetry||Hydrophobic interactions; hydrophilic interactions; salt bridges; hydrogen bonds; disulfide bonds||Globular; fibrous|
|Quaternary||Aggregates of two or more polypeptide chains to form biologically active protein||Hydrophobic interactions; hydrophilic interactions; salt bridges; hydrogen bonds; disulfide bonds|