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Chapter 5
Background
As discussed in section 1.5 it is already know from the literature that the accepted mechanism
of chaperonin function, involves the formation of cage like structures to trap a non native
protein within it. Exactly how the protein is then folded to its native state is still under debate
(Lin et al., 2008, England et al., 2008, Horwich et al., 2007, Chakraborty et al., 2010). What
is agreed upon however, is that the entrapment of the non native protein allows it to fold
without influence from other cellular structures (Ellis, 1994). One of the most widely studied
chaperonin is the E. coli GroEL. The mechanism by which this chaperonin functions has
already been discussed in section 1.5, but briefly, involves the formation of a stable double
ringed structure which can bind to and encapsulate its substrate proteins. Along with the help
of its cochaperonin GroES, the GroEL chaperonin then goes through a repeating cycle of
binding, folding and releasing the substrate in an ATP dependent manner (Horwich et al.,
2007).
It was surprising then, that in 2004, Qamra et al. showed that the chaperonins of M.
tuberculosis existed as lower oligomers and crystallised as dimers (Qamra et al., 2004,
Qamra & Mande, 2004). Since ATP hydrolysis is an integral part of the chaperonin reaction
cycle, it was also surprising to find that these chaperonins displayed very weak ATPase
activity (Qamra et al., 2004). They also claimed that the Mycobacterial chaperonins are
unable to complement in E. coli (Kumar et al., 2009). These findings were unusual, as it
suggested the possibility of M. tuberculosis chaperonins using a different mechanism to that
of GroEL to function. In chapter 3 however, it was shown that Cpn60.2 from M. tuberculosis
can function in E. coli. Although this does not prove the formation of a multimeric structure,
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