Chaperones, Molecular
493
increase in temperature. Unfolding of
proteins reintroduces all the potential
problems of misfolding and aggregation
that exist when the proteins are Frst
synthesized.
Molecular chaperones are proteins that
have evolved to deal with all these inherent
barriers to the cell’s need to have the
right proteins in the right place in their
active conformations. As later sections
will describe, they have been shown to
participate in all the examples given above,
and in their absence many of these
essential cellular functions cannot take
place at all. Some chaperones appear
to act predominantly by binding to and
preventing the aggregation of proteins that
have become unfolded; others are able to
actively promote folding of proteins that
otherwise cannot fold; and yet others can
act on aggregated proteins to unfold them
in order to allow them another opportunity
to refold.
3
Classifcation oF Molecular Chaperones
Molecular chaperones can be described in
terms of their cellular locations, their mode
of expression, their mode of action, and the
proteins or other molecules upon which
they act, but they are best classiFed in
terms of sequence similarity. Chaperones
that belong to a particular group deFned
thus turn out, unsurprisingly, to have
similar structures and act on similar
substrates through related mechanisms.
The mechanisms of action and structures
of
the
members
of
different
groups
a
r
eo
f
t
enq
u
i
t
ed
i
s
t
in
c
t
.T
h
ed
e
g
r
e
eo
f
sequence similarity within a group varies
between different groups: some molecular
chaperones are among the most highly
conserved of all proteins, whereas others
show very high heterogeneity between
members of the same group. It must
be remembered that sequence similarity
alone is only an indicator of potential
molecular chaperone activity, not proof of
it, and that direct experimental evidence
should
always
be
sought
to
conFrm
whether or not a given protein is indeed
acting as a chaperone.
The classiFcation of molecular chaper-
ones is complicated by a number of factors,
some of which are as follows:
– ±irst, certain proteins have been discov-
ered that do not themselves act directly
on protein substrates, but are required
for the full chaperone reaction to take
place. These are generally referred to as
‘‘cochaperones,’’ and as they are cen-
tral to the chaperoning process they are
usually discussed in the same context
as molecular chaperones.
–S
e
c
o
n
d
,t
h
ef
a
c
tt
h
a
to
f
t
e
np
r
o
-
teins from the same chaperone fam-
ily have been discovered and stud-
ied in different organisms or sev-
eral
different
cellular
locations
at
roughly the same time has led to
a proliferation of names for proteins
within
a
given
family,
which
can
be confusing.
– Third,
many
chaperones
are
heat-
inducible, and as they were often
Frst discovered by virtue of this prop-
erty, they are referred to as heat
shock proteins (HSPs). Unfortunately,
this means many chaperone families
are labeled as HSPs, even though
not all the proteins within that fam-
ily may be heat shock–inducible. An
alternative approach is to use the
names
of
the
best
studied
mem-
ber to label the group, but this is
equally unsatisfactory as the name
given to this protein may refer to
previous page 1167 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1169 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off