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Chapter 4
Discussion
The objective of this chapter was to try to expand on the knowledge of the functional and
oligomeric properties of M. tuberculosis chaperonins. In the last chapter the two chaperonins,
Cpn60.1 and Cpn60.2, were tested for their ability to function in E. coli in the absence of
endogenous GroEL. It was shown that while Cpn60.2 can complement for the loss of GroEL,
Cpn60.1 could not. As a result, and based on the data obtained from literature, it was accepted
that while Cpn60.2 may function as the main house-keeping chaperonin, it can be predicted
that Cpn60.1 has evolved to perform other functions (Hu et al., 2008, Kim et al., 2003, Ojha
et al., 2005, Qamra et al., 2005, Cehovin et al., 2010).
There could be various reasons as to how both these chaperonins are able to assist in different
cellular functions. One of these reasons could be that both of these M. tuberculosis
chaperonins are able to recognise and fold different groups of substrates. Since Cpn60.2 can
also function in E. coli, it suggested that Cpn60.2 can also recognise a large number of the
GroEL substrates, or at the very least the substrates that are vital for cell survival. A point to
note is that, GroEL has very broad substrate specificity as it interacts with a large number of
substrates in E. coli (Chapman et al., 2006).
It is already known that the apical domain of the chaperonins is where a potential substrate
first interacts with the chaperonins. It was reasoned that swapping the apical domain from
Cpn60.2 or GroEL into Cpn60.1 might allow it to recognise the same set of substrates as the
house-keeping chaperonins. This could then potentially lead to Cpn60.1 functioning in E.
coli. However, this assumed that Cpn60.1 would be able to fold these new substrates and
release them at the rate required by the cell.
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