residues exposed to the solvent. A small
intermediate domain connects the two
large domains. The intermediate segments
have some ﬂexibility allowing a hinge-
like opening of the apical domains, which
occurs upon nucleotide binding. These
movements are large and have been visual-
ized by three-dimensional reconstruction
from cryoelectron microscopy by Sebil and
GroES is a heptamer of 10 kDa subunits
forming a ﬂexible dome-shaped structure
to accommodate proteins up to 70 kDa.
-sheets and ﬂexible
loop regions. The loop regions are critical
for the interactions between GroEL and
GroES. It was deduced from electron
microscopy studies that GroES binding
to GroEL induces large movements in
the apical GroEL domains. This provokes
of the central cavity in which protein
folding proceeds. NMR coupled with the
study of hydrogen-exchange techniques
essentially unfolded in their GroEL-bound
states. Mass spectroscopy has revealed
the presence of ﬂuctuating elements of
secondary structure for several proteins.
recognizes nonnative proteins.
The reaction cycle of the GroEL–GroES
through hydrophobic interactions. Then,
the equatorial domain of the same ring
binds ATP, and GroES caps the upper
ring, sequestering the protein inside the
internal chamber in which the protein
folding proceeds. The binding of GroES
induces a conformational change in GroEL
and ATP hydrolysis, which is a cooperative
process that produces a conformational
change in the lower ring, allowing it
to bind a nonnative protein molecule.
ATP and GroES in the lower ring, and
the dissociation of the upper complex,
releasing the protein and ejecting GroES.
If the protein has not reached the native
state, it is subjected to a new cycle.
The reaction cycle of GroEL–GroES. Inf
is the unfolded protein, N the folded one, A is
the apical domain, (in blue), I the intermediate
domain (in red) and E the equatorial domain (in
magenta). (Reproduced from Wang & Weissman
Nat. Struct. Biol.
, 597, with permission.)
(See color plate p. xxii).