Aggregation, Protein
The association of nonnative protein molecules through intermolecular hydrophobic
Amyloid Fibrils
Ordered aggregates.
Inclusion Bodies
Insoluble, amorphous, disordered aggregates.
Molecular Chaperones
Proteins that assist protein folding within cells.
Protein Folding
The process by which polypeptide chains acquire their three-dimensional and
functional structure.
Three dimensional–Domain Swapping
An aggregation mechanism in which one domain in a multidomain protein is swapped
with the same domain of another molecule.
Protein misfolding and aggregation are frequent phenomena that occur under
different conditions
in vivo
as well as
in vitro
affecting both the production of proteins in the biotechnology and pharmaceutical
industries and human health. The aggregates are formed from nonnative proteins
through intermolecular interactions that compete with intramolecular interactions.
There is thus a kinetic competition between proper folding and misfolding, which
can generate aggregates.
Recent evidence for transient association of intermediates during
in vitro
has been obtained for several monomeric proteins. Irreversible and insoluble
aggregates are formed in an off-pathway folding process; their formation is
concentration dependent and could be prevented by using very small protein
concentrations. These aggregates can dissociate and dissolve only in the presence of
high concentrations of denaturant. The mechanisms involved in these aggregation
processes will be discussed in light of the so-called
new view
of protein folding.
The environmental conditions within cells are markedly different from those
used in
in vitro
refolding studies. In the production of recombinant proteins in
foreign hosts, the formation of disordered aggregates, that is, inclusion bodies, is
often observed. However, aggregation can also result in the formation of amyloid
Fbrils, which are ordered aggregates. These amyloid formations are at the origin of
serious diseases.
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