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

Chapter 1
As protein folding in Mycobacterium tuberculosis is the subject of this thesis, it is interesting
to note that in M. tuberculosis and other actinomycetes, horizontal gene transfer has resulted
in the acquisition of the 20S proteasome. Structurally it is composed of two rings of catalytic
β subunits sandwiched by rings of α subunits making a barrel like structure (Hu et al., 2006).
The eukaryotic 26S proteasome consists of a 20S core flanked on one or both sides with a
19S ATPase cap. This cap is responsible for the recognition, unfolding and translocation of
the ubquitinated substrate into the 20S chamber for degradation. In actinomycetes however,
this function is performed by homologous ATPases like Mpa (Mycobacterium proteasome
ATPase) or ARC (AAA ATPase forming Ring-shaped Complex) (Pearce et al., 2008, Wolf et
al., 1998). While the eukaryotic protease system uses ubiquitin to recognise appropriate
substrates for degradation, in M. tuberculosis it has been shown that Mpa recognises
substrates that have small ubiquitin like proteins attached called Pup (prokaryotic ubiquitinlike
protein) (Pearce et al., 2008, Striebel et al., 2009a, Burns et al., 2009). An interesting
point to note here is that although a large number of proteins (58 currently identified targets,
including Cpn60.2 and Cpn10) in M. tuberculosis have pupylation sites, not all of them
become proteasome substrates (Festa et al., 2010). More in depth information about the
Cpn60 family of chaperones is available in section 1.5. A cartoon representation of the
protease degradation process can be seen in figure 1.4 below.
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