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

Chapter 1
main difference between the eight subunits is present in the sequence of the apical domains
which have specific interactions with unfolded proteins (Spiess et al., 2006). Two of CCTs
best studied specific substrates are the cytoskeletal proteins actin and tubulin. Both of these
have been shown to interact specifically with select subunits from the CCT complex (Llorca
et al., 1999). As is the case with the thermosomes, it is the protrusions that are present on the
apical domain that fold to cover the openings of the chaperonin and form the dome structure.
EM analysis of asymmetrically arranged subunits revealed that the position of the subunits
was directing a sequential mechanism of ATP binding and hydrolysis within the ring, unlike
GroEL (Rivenzon-Segal et al., 2005).
Although the exact mechanism of substrate folding by CCT is not yet fully understood, recent
crystal structures have provided a lot of information about the nature of the residues on and in
the CCT complex (Cong et al., 2010). It has been shown that, like GroEL and thermosome,
the inner surface of the closed chamber of CCT is also very hydrophilic but varies in charge
distribution. The inner chamber of GroEL is a lot more negatively charged, while CCT has
been shown to be predominantly positively charged. These differences in the charged
properties of CCT have been suggested to be related to its ability to fold some substrates that
cannot be folded by other chaperonins. These results implicate polar and electrostatic
interactions in substrate binding; however, hydrophobic interactions have also been shown to
occur (Rommelaere et al., 1999, Yam et al., 2008).
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