Chaperonin—Co-chaperonin Interactions - The Networking of Chaperones by Co-chaperones - page 160

Fig. 8.4 The GroEL/GroES folding cycle. The binding of substrate to one GroEL ring is followed
by the binding of ATP and GroES to the cis ring. The substrate is released into the cavity closed by
GroES and allowed to fold. ATP is hydrolysed and the complex is ready to dissociate. The binding
of ATP to the trans ring triggers release of substrate and dissociation of GroES from the cis ring
and allows GroES to bind releasing substrate into the cavity
then forms a lid over the central cavity entrapping the protein. GroES binding is
faster than ATP-induced release of the substrate and this provides a mechanism
for the entrapment of proteins in the cis cavity (Burston et al. 1995 ). The complete
GroEL/GroES folding cycle is shown in Fig. 8.4 .
The transition between the open conformation, that is receptive to protein bind-
ing, and the closed state, in which the protein is isolated, is induced by ATP binding
and hydrolysis (Horovitz and Willison 2005 ). ATP binds with positive cooperativity
within rings but with negative cooperativity between rings (Yifrach and Horovitz
1995 ). Allosteric transitions support the ATP-dependant control of the affinity of
GroEL for its substrate and the subsequent folding (Saibil et al. 1993 ; Roseman
et al. 1996 ; Yifrach and Horovitz 1995 ). ATP binding initiates bending and twisting
of subunit domains that distorts the ring structure. ATP binds to a ring with positive
cooperativity, and movements of the interlinked subunit domains are concerted.
In contrast, there is negative cooperativity between the rings, so that they act in
alternation (Rye et al. 1997 ; Horovitz et al. 2001 ). Understanding the pathways of
allosteric communication in GroEL has been the subject of intense research, and
this was viewed more recently by (Saibil et al. 2013 ).
Once the substrate is encapsulated in the chamber, the slow rate of ATP hydro-
lysis dictates the length of time for folding to take place, however ATP hydrolysis
is not required for protein folding but is required to complete the reaction cycle