Hi, my name is Jason Young from
McGill University, and I'll be presenting
an overview of eukaryotic molecular
chaperones in the cytosol.
Proteins are synthesized
as linear polypeptides and
must fold into complex three-dimensional
structures to become functional.
The folded functional conformation of
a polypeptide is the native state.
The basis of protein folding is that
the native conformation of a polypeptide
is determined by its primary
amino acid sequence.
Folding can start with a polypeptide
in an extended unfolded state.
As folding proceeds,
the polypeptide becomes increasingly
compact until it reaches the native state.
Protein folding is driven by
hydrophobic interactions, so
that in the native state most hydrophobic
amino acids are sequestered within
the center of the protein, and hydrophilic
amino acids around the surface.
However, intermediates on the folding
pathway can still have significant levels
of exposed hydrophobic regions.
Protein folding in the cell is
complicated by a number of factors.
The cellular environment is highly crowded
with macromolecules which increases
the rates and affinities of
interactions within a polypeptide, but
also between different polypeptides.
Also, multiple unfolded proteins can be
present at the same time inside a cell.
This leads to an increased risk
of protein aggregation, that is,
non-productive interactions between
unfolded polypeptides can cause
the polypeptides to become insoluble.
Plaques of insoluble polypeptides
have been linked to a number of
neurodegenerative diseases, including
Alzheimer and Parkinson's syndromes.
Furthermore, new polypeptides must be
folded vectorially, as they are translated
on ribosomes, while mature proteins
that are denatured by stress conditions,
such as heat shock, must be refolded.
Therefore, cells have developed
a system of molecular chaperones,
which prevent protein aggregation and
assist the folding of proteins.