Transitions with the native state are slow and cooperative, those with
the unfolded state fast and noncooperative.Characteristics and significance of the molten globule state are still a matter
of debate.
- In many cases,refoldingto the native state isincompleteor not
precise. For many proteins, the peptide chain produced in the cell assumes
its native folded state with the aid of specific helper proteins, called
chaperonins. These are missing when a protein has been denatured and is
allowed to refold in practice. Several proteins refold into a near-to-native
state, which then may or may not slowly change into the native
conformation.
In conclusion, proteins are individuals. Although the same factors
determine the conformation and the conformational stability, the net result
is highly variable. Moreover, they react in a different way on differences in
environmental conditions, which is further illustrated below.
7.2.2 Denaturation
Because of the relatively small stability of most globular proteins, they can
be induced to unfold in many ways. If the conditions causing unfolding
(high temperature, extreme pH, etc.) are removed again, the ultimate result
will depend on the extent to which the peptide chain will regain its native
conformation and possibly on the rate of this refolding. Reactions occurring
when the protein is in the unfolded state may partially prevent this.
Prevention of refoldingto the native state can be caused by several
reactions, but this has been studied insufficiently. The following ones may be
involved.
- Aggregationof the unfolded molecules. Upon unfolding, many
hydrophobic residues become exposed, which generally leads to a
substantially decreased solubility. This would undoubtedly cause refolding
to be slower, but it is uncertain whether it would be prevented. It may well
be that intermolecular cross-linking is involved (points 3 and 5), since this
may occur much faster when the molecules are already aggregated due to
noncovalent bonding. - Trans?cischange of the configuration of peptide bonds. The
trans conformation is very stable, except for a peptide bond involving the N
of proline