Primary Structure of Proteins

The amino acid sequence (the primary structure) of a protein determines its three-dimensional structure, which, in turn, determines its properties. In every protein, the correct three-dimensional structure is needed for correct functioning.

Why is it important to know the primary structure?

One of the most striking demonstrations of the importance of primary structure is found in the hemoglobin associated with sickle-cell anemia. In this genetic disease, red blood cells cannot bind oxygen efficiently.

The red blood cells also assume a characteristic sickle shape, giving the disease its name. The sickled cells tend to become trapped in small blood vessels, cutting off circulation and thereby causing organ damage.

These drastic consequences stem from a change in one amino acid residue in the sequence of the primary structure. Considerable research is being done to determine the effects of changes in primary structure on the functions of proteins.

Using molecular-biology techniques, such as site-directed mutagenesis, it is possible to replace any chosen amino acid residue in a protein with another specific amino acid residue.

The conformation of the altered protein, as well as its biological activity, can then be determined. The results of such amino acid substitutions range from negligible effects to complete loss of activity, depending on the protein and the nature of the altered residue.

Determining the sequence of amino acids in a protein is a routine, but not trivial, operation in classical biochemistry. It consists of several steps, which must be carried out carefully to obtain accurate results (Section).