494
Chaperones, Molecular
the phenotype through which the pro-
tein was frst discovered, and which
may be quite specifc to a particu-
lar organism.
– Fourth, the name ‘‘molecular chap-
erone’’ is used in a very catholic
sense to re±er to any protein with the
properties listed in Sect. 1 above, but
these may range ±rom extremely broad-
spectrum chaperones, which act on a
large range o± substrates to those that
have evolved to act with only one specifc
substrate.
– Fi±th, many proteins are un±ortunately
described as molecular chaperones with
only minimal supporting evidence ±rom
in vitro
and
in vivo
studies.
The Table 1 is not intended to be
comprehensive, but illustrates the major
known ±amilies o± molecular chaperones,
together with the names o± some o± their
better-studied members, their cellular lo-
cations, and a very brie± description o±
their properties. The individual molecu-
lar chaperone ±amilies shown in the Table
are discussed more ±ully in the ±ollow-
ing sections.
4
Mechanisms and Roles of the Major
Molecular Chaperones
4.1
The Hsp60 Family
4.1.1
Introduction to the Hsp60 Family
The Hsp60 ±amily is one o± the best
characterized o± the molecular chaperone
±amilies. It is a large ±amily consisting
o± highly similar proteins, all with a sub-
unit molecular mass o± around 60 kDa.
Sequence comparisons have enabled the
division o± the Hsp60 ±amily into two
groups: Group I and Group II. The Group
I proteins are ±ound in nearly all bacteria,
and also in mitochondria and chloroplasts.
Th
eG
roupI
Ip
ro
t
e
in
sa
r
e±oundina
r
-
chaea, and in the eukaryotic cytosol. All
these proteins have a remarkable multi-
meric structure: Group I proteins assem-
ble into a ‘‘double doughnut’’ structure
with seven subunits in each ring, and the
Group II proteins assemble into a similar
structure but with eight or nine subunits
in each ring, depending on the particular
protein and organism. Each ring encloses
a cavity or cage. Proteins in the Hsp60
±amily are o±ten re±erred to generically as
‘‘chaperonins.’’
4.1.2
Cellular Roles of the Hsp60 Family
The Group I ±amily o± the Hsp60 proteins
has been the most intensively studied, par-
ticularly the protein ±rom
Escherichia coli
,
which is re±erred to as GroEL. Genetic
evidence shows that these proteins are
essential, both in prokaryotes and eukary-
otes, and they are ±ound in all organisms
so ±ar studied, with the exception o± some
mycoplasmas. They are present at ±airly
high levels in cells (
E. coli
is estimated
to contain around 2000 GroEL complexes
per cell under normal growth conditions)
and are ±urther induced by heat shock.
All o± them appear to require a cochap-
erone, called Hsp10, which is a smaller
protein o± typically around 10 kDa, which
itsel± assembles into a ring with seven-
±old symmetry. In
E. coli
, this protein is
called GroES, and in
E. coli
and most
other bacteria it is encoded in the same
operon as the GroEL protein and is also
essential.
I± the levels o± GroEL become too
low to sustain cellular growth, or i± a
temperature-sensitive mutant is shi±ted to
the nonpermissive temperature, a large
subset o± cellular proteins ±ails to ±old
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