Proteins
commonly produce their actions by recognizing and binding to other molecules,
and for these interactions to occur, the shape of the protein must match the
shape of the other molecule. This may be exemplified by the interaction of an
antibody protein and an antigen, and between the opioid receptor protein and
morphine or heroin.
All
proteins have three and sometimes four levels of structures: the primary
structure consists of a simple chain of amino acids arranged in a linear
fashion; the secondary structure has folding or coiling within the protein
structure; the tertiary structure is the three-dimensional shape of a folded
protein; a quaternary level is when two or more peptides are joined together to
form a single large protein. Proteins are only able to function biologically
when their chains are folded into threedimensional shapes.
From
the mid-1950s, Christian Anfinsen, an American biochemist at the National
Institutes of Health, studied the relationship between protein structure and
its function. For this purpose, he selected the protein ribonuclease, an enzyme
that breaks down ribonucleic acid (RNA). Ribonuclease is stable, of small size,
well studied, and readily available in purified form from commercial sources.
In 1957, Anfinsen determined that after the three-dimensional structure of
ribonuclease was disrupted and lost its biological activity, it spontaneously
refolded and returned to its native (normal), fully functional shape, with its
enzyme activity restored. Many other proteins respond in the same manner as
ribonuclease.
From
these experiments, Anfinsen concluded that the information required by a
protein to assume its final three-dimensional configuration is encoded in its
primary structure—namely, its amino acid sequence. Moreover, according to
Anfinsen’s “thermodynamic hypothesis,” ribonuclease assumes this
three-dimensional structure because this structure is most stable. In 1972,
Anfinsen was awarded the Nobel Prize in chemistry for establishing a connection
between the amino acid sequence of a protein and its biologically active shape.
A
number of diseases—as Alzheimer’s, Parkinson’s, and Huntington’s—have been
associated with an accumulation of misfolded proteins, all of which are thought
to have an amyloid protein origin, increase with age, and may have a genetic
basis.
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