Chemistry Reference
In-Depth Information
Specific Functions of Bacterial Co-chaperonins
In addition to co-chaperonin activity, a number of diverse roles played by bacterial
co-chaperonins are emerging, in particular during host-pathogen interactions. The
possible reasons for numerous chaperonins in bacteria were reviewed by Lund in
2009 and the evolution of so many different functions were highlighted by Henderson
and Martin (
2011
; Henderson and Martin
2011
; Lund
2009
). Most bacterial Cpn10
proteins are stimulators of the immune system and the response varies between dif-
ferent species, with human and
E. coli
Cpn10 proteins being poor immunogens and
M. tuberculosis
and
M. leprae
being strong immunogens (Cavanagh and Morton
1994
). These proteins also play a role in apoptosis, cytokine secretion and cellular
growth and development (Cavanagh
1996
). Cpn10 of
M. tuberculosis
, a secreted
protein with cell signalling functions, is an important virulence factor during infec-
tion and it plays a key role in the pathology of spinal tuberculosis by inhibiting the
growth of osteoblasts (Meghji et al.
1997
; Roberts et al.
2003
). Structures have been
reported for
M. leprae
, and
M. tuberculosis
cpn10 proteins and immunodominant
epitopes have been mapped to the mobile loop (Mande et al.
1996
; Roberts et al.
1999
). Further structural analysis of
M. tuberculosis
Cpn10, in the presence of di-
valent cations, showed the existence of a heptamer (Taneja and Mande
2001
,
2002
).
The crystal structure of
T. thermophilus
HB8 Cpn10 showed disordered loops in
five subunits (Numoto et al.
2005
). Comparison of
M
.
tuberculosis
Cpn10 to that of
T. thermophilus
HB8 Cpn10 revealed a similar overall structure, however the dome
loops and mobile loops are different (Fig.
8.5
). The Cpn10 from
Aquifex aeolicus
has a 25-residue C-terminal extension present in each monomer that is absent from
Fig. 8.5
The overall structures of
M. tuberculosis
Cpn10 (
a
) and
T. thermophilus
Cpn10 (
b
) con-
form to the GroES-fold. Differences are evident in the mobile loops and a partially helical structure
is present in the
T. thermophilus
Cpn10 monomer. Breaks are evident in the structures due to a
lack of electron density in the highly flexible mobile loops. Alpha helices are shown in
red
and
ʲ-sheets in
yellow
. The images were generated using PyMol (DeLano Scientific) from coordinates
in PDB: 1HX5 and WNR
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