mohammad tabish ahmed - eTheses Repository - University of ...

Chapter 1
result the substrate protein is rapidly disassociated and pushed into the central cavity to fold
(Horwich et al., 2006, Rye et al., 1997, Chaudhry et al., 2003, Xu et al., 1997). It is however
agreed upon that GroES acts as the lid to seal off the GroEL cavity to allow a protein to fold
without being influenced by the crowded nature of the cell. However, the mechanism
involved in the folding of proteins within the cavity is also subjected to further debate.
1.5.4.2 GroEL and GroES function
The mechanism of action of GroEL and its cochaperonin is now understood in detail. As
discussed above, GroES forms a homo-heptameric ring that caps one of the two GroEL rings
forming an asymmetric complex (Horwich et al., 2007, Bochkareva et al., 1992, Burston et
al., 1995). This binding of GroES, displaces any bound substrate into the cavity of GroEL so
the reaction cycle can continue. There are 3 states in which GroEL and GroES can be found
during the reaction cycle (Ranson et al., 1997):
1- The acceptor state (open state): In this state one ring of GroEL bind to the substrate
(client protein) while the other ring remains bound to ADP and GroES.
2- The encapsulation state (closed state): In this state the substrate is released into the
cavity to fold under hydrophilic conditions. This occurs when GroES and ATP bind to
the same ring as the substrate.
3- The ejection state (release state): In this state the folded/semi folded protein along
with GroES is released from GroEL. This occurs when the bound ATPs are
hydrolysed and allows another 7 ATP molecule to bind to the second ring, followed
by substrate and GroES binding.
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