Proteins

Domains are large functional regions of the protein, such as an enzyme's active site, which binds the substrate to the enzyme. Myoglobin, the muscle protein that stores and releases oxygen, contains several alpha-helices wound around a central crevice. It is in this central crevice that the O₂ molecule binds. Just as words take on their meanings when completed, the functional domains unite to form the overall purpose of a protein. For example, a membrane protein stabilizes itself by anchoring itself with a hydrophilic cytoplasmic domain, then weaves its alpha-helices throughout the membrane domain and projects its carbohydrate hydrophilic side chains into the extracellular surface domain. Such membrane proteins often act as receptors, important for receiving signals such as hormones, or work in the immune system to recognize infected cells.

The local foldings, evident in secondary structure, then combine into a single polypeptide chain. This chain is called the tertiary structure, or conformation. For example, the pancreatic enzyme ribonuclease, which aids in digestion of RNA in the diet, consists mainly of beta sheet folds, with three small alpha-helical regions. Tertiary structure is often stabilized by disulfide bonds between adjacent cysteine in different regions of the protein. For example, the tertiary structure of ribonuclease contains four disulfide bonds, located at specific sites. The stability of the tertiary structure of proteins is destroyed by toxic heavy metals such as mercury. Concentrations of mercury in the environment, for example, result in the displacement of hydrogen on the sulfur atom (SH), thereby blocking functional disulfide bonds.

Several other weak, noncovalent interactions also help stabilize tertiary structure. These noncovalent interactions can be disrupted by heating a protein or exposing it to extremes in pH (acidity or alkalinity), which alters the charge of polar groups on the amino acids. Such disruptions cause the protein to unfold, often exposing hydrophobic groups and leading to precipitation (clumping together) of the protein. If these disruptive factors are removed, some proteins can refold to their original conformation. This ability to refold confirms that protein folding is a self-assembly process that is dependent upon the sequence of amino acids.

Peptide bond formation. Adapted from Robinson, 2001.