Chaperones, Molecular
Unfolded Protein
Any protein that is not in its fully folded state. This term encompasses a large range of
possible states, from a protein that is nearly but not completely native to one that is a
random coil.
Some proteins in the cell are needed to help other proteins reach their Fnal active
conformations: these are referred to as molecular chaperones. Molecular chaperones
can be grouped into families by sequence similarity, and they act through a variety
of mechanisms. They are found in all cell types and in most locations within the cell.
Many are induced by stresses such as heat shock. This chapter will review the reasons
why molecular chaperones are required in the cell, and then discuss each of the
major families of molecular chaperones in turn, in terms of structure, mechanism
of action, and cellular role. Most molecular chaperones act in networks with other
chaperones, and some of these will be reviewed. Many molecular chaperones interact
with a broad range of different substrates, but some are speciFc to particular proteins,
and examples of these will be discussed.
The Defnition oF a Molecular Chaperone
The number and range of proteins now
classiFed as molecular chaperones are very
large, and a deFnition that encompasses
all of them is likely to be so vague as to
be uninformative. Molecular chaperones
must, however, have two properties in
order to be deFned as such, which are
as follows:
1. They must assist other molecules to
reach their Fnal active state, by blocking
or reversing unfavorable events that
would otherwise prevent this state from
being reached.
2. They must not be part of the Fnal
active structure whose existence they
have helped to create.
originally coined to refer to the protein
nucleoplasmin, which is required for
the correct assembly of nucleosomes,
and the choice of the term ‘‘chaperone’’
is based on the conventional use of
the word, to refer to a person who
prevents inappropriate interactions from
occurring that could hinder an otherwise
desirable outcome. (The etymology of
the word ‘‘chaperone’’ is of interest:
‘‘chaperonner,’’ which means ‘‘to protect.’’
This, in turn, was
originally derived
from the Old ±rench noun ‘‘chaperon,’’
which meant ‘‘a protective hood’’). The
justiFcation for this choice of name is
that for biological molecules such as
proteins, getting from the state where
they are Frst synthesized to the state
where they are Fnally active (folded, and
in the correct cellular compartment) is
a complex process during which many
unfavorable interactions can take place.
These, if they were allowed to occur,
would drastically lower the efFciency with
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