Molecular Chaperones

Tittle: Biological Importance of molecular chaperones in protein folding.

Aim: To investigate what are molecular chaperones, how they function

and what is their role.

Introduction
In molecular biology, molecular chaperones are proteins that assist the
covalent folding or unfolding and the assembly or disassembly of other
macromolecular structures. Chaperones are present when the
macromolecules perform their normal biological functions and have
correctly completed the processes of folding and assembly. The
chaperones are concerned primarily with protein folding [1]. The first
protein to be called a chaperone assist the assembly of nucleosomes from
folded histones and DNA and such assembly chaperones, especially in the
nucleus, are concerned with the assembly of folded subunits into
algometric structures. One major function of chaperones is to prevent
both newly synthesised polypeptide chains and assembled subunits from
aggregating into non-functional structures. It is for this reason that many
chaperones, but by no means all, are heat shock proteins because the
tendency to aggregate increases as proteins are denatured by stress. In
this case, chaperones do not convey any additional steric information
required for proteins to fold [3]. However some highly specific steric
chaperones do convey unique structural (steric) information onto proteins,
which cannot be folded spontaneously. Such proteins violate Anfinsen
dogma, requiring protein dynamics to fold.

Body
There are many different families of chaperones. Each family act to aid
protein folding in a different way. In bacteria like E.Coli, many of these
proteins are highly expressed under conditions of high stress. For
example, when the bacterium is placed in high temperatures. For this
reason, the term heat shock proteins has historically been used to name
these chaperones [4]. For many proteins, completion of folding requires
the subsequent interaction with one of the large oligomeric ring-shaped
proteins of chaperon in family, which is composed of the GroEL like
proteins in eubacteria, mitochondria and chloroplasts, and the the TRiC
family in eukaryotic cytosol and archae. Molecular chaperones in the
eukaryotic cytosol were shown to interact differently with chemically
denatured proteins and their newly translated counterparts. Other types
of chaperones are involved in transport across membranes, for example
membranes of the mitochondria and endoplasmic reticulum in eukaryotes.
Bacterial translocation-specific chaperones maintain newly synthesised
precursor polypeptide chains in a translocation competent (generally
unfolded) state and guide them to the translocon. Molecular chaperones
have an essential role in the regulation of protein conformation states- the
process during which translent or stable interactions with client proteins
affects their conformation and stability. Chaperones capture unfolded
polypeptides, stabilise intermediates and prevent misfolded species from
accumulating in stress cells. The capacity of the Hsp70 and Hsp90
chaperones to regulate these processes involves a constellation of
positives and negative co-chaperones that function in various
combinations to interact with chaperones to relate folded proteins, to
facilitate the assembly or disassembly or chaperone-containing
neteromeric complexes [2]. A large number of neurodegenerative
diseases in humans result from protein misfolding and aggregation.
Protein misfolding is believed to be the primary cause of Alzheimers
disease, Huntingtons disease, Creutzfeldt-Jakob disease and many other
degenerative and neurodegenerative disorders. Cellular molecular
chaperones, which are ubiquitous, stress-induced proteins, and newly
found chemical and pharmacological chaperones, have been found to be
effected in preventing misfolding of different disease-causing proteins,
essentially reducing the several neurodegenerative disorders. Functional
aspect of the different types of chaperones suggests their uses as
potential therapeutic agents against different types of degenerative
diseases, including neurodegenerative disorders [3].

Conclusion
Many chaperones are heat shock proteins, that is, proteins expressed in
response to elevated temperatures or other cellular stresses. The reason
for this behaviour is that protein folding is severely affected by heat and
therefore, some chaperones act to prevent correct damage caused by
misfolding. Other chaperones are involved in folding newly made proteins
as they are extruded from the ribome. Although most newly synthesised
proteins can fold in absence of chaperones, a minority strictly requires
them for the same
References

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SOD1 form aggregate structures with distinct molecular properties
in human cells . J Biol Chem. 281: 4477-4485 (2006)
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