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

Chapter 1
The exact mechanism of the reaction cycle is still under investigation, but based on the
reports so far it is possible to suggest that the thermosome interaction with ATP may be as
follows:
1. ATP binding to one ring on the thermosome results in the opening of the cavity. The
asymmetric nature of the rings results in the ATP affinity of the second ring to drop.
2. ATP hydrolysis on the first ring then results in large conformational changes that
result in the substrate being released into the central cavity for the folding process
while the lid closes the cavity.
3. At this stage, owing to negative cooperativity, the opposite ring can bind to ATP and
maintain asymmetry. It has also been suggested that the dissociation of the product is
required before ATP hydrolysis can occur on the second ring.
1.5.3.2 Eukaryotic CCT
CCT is a complex ATP dependent chaperonin as it possesses eight different but homologous
subunits in each of its two rings which are referred to as α, β, γ, δ, ε, δ, ε, and ζ (Kubota et
al., 1995, Kubota et al., 1994). The entire structure is made up of two barrel shaped double
ring cylinder which is approximately 160Å in height and 150Å in diameter (Llorca et al.,
1999) (Fig 1.17). Each of these eight subunits is encoded by eight specific genes. Although
the presence of eight different subunits could result in a very large number of possible
arrangements, the presence of preferential inter-subunit contacts ensures that the position of
each subunit within each ring is highly specific in arrangement and is shared between all
CCTs (Liou & Willison, 1997) (fig 1.17a). It has also been shown that these subunits are
always in the same phase with the opposite ring (Martin-Benito et al., 2007) (fig 1.17b). The
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