Primary Structure of Proteins
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
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.
research is being done to determine the effects of changes in primary structure
on the functions of proteins. Using molecular-biology tech-niques, 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.
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.
following Biochemical Connections box describes an important practi-cal aspect
of the amino acid composition of proteins. This property can differ markedly,
depending on the source of the protein (plant or animal), with important
consequences for human nutrition.
The primary structure of a protein determines
the other levels of structure.
amino acid substitution can give rise to a malfunctioning protein, as is the
case with sickle-cell anemia.