Chaperones, Molecular
transferred to another chaperone system,
such as the Hsp70/Hsp40 system. This
is discussed further below, in Sect. 5.2.1.
ATP is not required for any of this to occur,
further supporting the idea that sHSPs
are ‘‘holders’’ rather than ‘‘folders.’’ The
way in which protein is discharged is not
clear, but it may be related to changes in
oligomerization and hydrophobicity that
occur at different temperatures.
Structure and Function of sHSPs
The sHSPs form oligomers of variable
size with fewer than 10 to more than 50
subunits. Moreover, when complexed with
bound substrate proteins, their structure
and degree of oligomerization may be
signiFcantly different from when they have
no substrate bound. Several structures
have been obtained of free sHSP, and
all show oligomers formed roughly into
a hollow sphere. The binding sites for
unfolded proteins on the sHSPs have
not been determined, and there is no
detailed structural information for an
sHSP-substrate complex.
Chaperones and Cellular Processes
A complete understanding of the role of
chaperones in the cell is still some way
off, but recent work has improved our
understanding not only of the individual
families of chaperones but also of how they
interact with one another and in what way
their activities are required for the survival
and growth of healthy cells, both under
normal and under stressed conditions.
The following sections will examine some
examples of chaperones and chaperone
networks, which are employed for various
different processes in the cell. This is not
by any means a comprehensive list, but
should give at least a flavor of the ways
in which chaperones are involved in many
different aspects of cell growth.
Chaperones and Redox Potential
Chaperones have a key role in enabling
the cell to maintain active proteins under
a variety of redox states, in at least two
ways. ±irst, they are directly involved
in ensuring that proteins that require
disulFde bonds for their activity form those
bonds quickly and efFciently. Proteins
that catalyze the reactions that make or
break disulFde bonds in proteins are very
important in maximizing the yield of active
folded protein in cells, and many also
can act as chaperones on substrates that
lack cysteine residues. Second, chaperones
exist that are activated by anomalous redox
states to help chaperone the folding of
those proteins that may themselves have
become nonfunctional due to exposure to
these states.
Disul±de Bond Formation and
Isomerization in Prokaryotes and
The formation of disulFde bonds in
prokaryotes takes place in normal cir-
cumstances in the periplasm, the space
between the inner and outer membranes
in Gram-negative bacteria. (Gram-positive
bacteria that have only a single mem-
brane produce very few disulFde-bonded
proteins, although interestingly they do ex-
press proteins capable of catalyzing disul-
Fde bond formation). There is a signiFcant
difference between the redox states of the
cytosol (which is highly reducing) and
the periplasm (which is oxidizing), and
it was originally thought that this differ-
ence was sufFcient to allow disulFde bond
formation to occur at a reasonable rate.
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