Chaperonin—Co-chaperonin Interactions - The Networking of Chaperones by Co-chaperones - page 162

which possesses a single operon-encoded groEL gene with a groES gene, nearly
30 % of all bacterial genomes contain multiple chaperonin genes (Lund 2009 ). The
mycobacteria were the first bacteria revealed to have multiple chaperonins (Lund
2001 ; Kong et al. 1993 ). M. tuberculosis encodes two chaperonin genes, cpn60.1
in an operon with the co-chaperonin gene cpn10 and cpn60.2 in a different position
on the chromosome (Kong et al. 1993 ), while M. smegmatis has 3 copies of cpn60
(Fan et al. 2012 ). In bacteria with multiple groEL genes, such as mycobacteria,
the essential copy is unexpectedly often not the operon-encoded gene and this has
resulted in much interest and speculation about the functions of these additional
chaperonins (Hu et al. 2008 ; Ojha et al. 2005 ). It is possible that one copy preserves
the essential chaperone function, while the others diverge to take on altered roles
(Lund 2001 ). Biophysical studies of the chaperonins from M. tuberculosis and M.
smegmatis provide support of novel functions for Cpn60.1 as Cpn60.2 proteins as-
semble into oligomers and are able to replace GroEL in E. coli when co-expressed
with GroES or the cognate Cpn10; while neither Cpn60.1 nor Cpn60.3 found in M.
smegmatis could functionally replace GroEL (Fan et al. 2012 ). Based on the fact
that Cpn60.1 appears to chaperone a discrete set of key enzymes involved in the
synthesis of the complex cell wall and differences in protein sequence, this novel
mycobacterial chaperonin may provide a unique target for drug development [re-
viewed by (Colaco and MacDougall 2014 )].
One of the five GroEL paralogs in Sinorhizobium meliloti is required for NodD
protein folding (Ogawa and Long 1995 ), whilst Bradyrhizobium japonicum possess
at least five groESL operons that can partially compensate for the lack of one or
other genes (Fischer et al. 1993 ). These duplicated proteins have evolved specific
roles in different bacteria but the mechanism involved in functional divergence has
not been elucidated (Wang et al. 2013 ). Myxococcus xanthus DK1622 displayed
functional divergence with respect to substrate specificity and this was as a re-
sult of differences in the apical and C-terminal regions of the two GroEL proteins
(Wang et al. 2013 ). Interestingly, monomeric Cpn60 from Thermus thermophilus
was able to support protein folding independently of both ATP and a co-chaperonin
(Taguchi et al. 1994 ). The crystal structures of the T. thermophilus Cpn60/Cpn10
complex alone (Shimamura et al. 2003 ) and with bound proteins has been reported
(Shimamura et al. 2004 ). Despite a destabilised structure, Cpn60 proteins from M.
tuberculosis also displayed activity in the absence of ATP or co-chaperonin (Qamra
and Mande 2004 ).
Cpn60s are dominant immunogens present during human bacterial infections.
Moreover, Cpn60s of M. tuberculosis are potent inducers of host inflammatory re-
sponses and behave as antigens and cytokines (Qamra et al. 2005 ). The host immune
response to exogenous chaperonins may be both protective and damaging (Ranford
and Henderson 2002 ). It has been hypothesised that due to sequence conservation,
the host immune response mounted against bacterial co-chaperonins may result in
cross-reactivity to human Cpn60 causing an autoimmune reaction (van Eden et al.
1998 ). There is convincing evidence for the case in the development of atherosclerosis
(Wick 2006 ). The roles of chaperonins in disease, including models and potential
treatments are addressed in a review by (Ranford and Henderson 2002 ).