Academic Projects:
1. Structure function analysis of M. tuberculosis heat shock proteins
(Collaborator: Abhijit A. Sardesai)
We have been interested in the overall properties of the M. tuberculosis HSPs, not that these are likely to be different than those of other well-studied prokaryotes. However, recent literature suggests that the HSPs play an important role in the pathogenesis of M. tuberculosis, and therefore our interest in this family of proteins. Our focus till now has been on the Hsp10 (GroES or Cpn10) and the two Hsp60’s (GroEL-1/ GroEL-2 or Cpn60.1/ Cpn60.2). We have also initiated studies towards biophysical and structural characterization of the two major heat shock repressors: HspR and HrcA.
|
Accumulation of
negatively charged residues suggested binding site for divalent cations, later
demonstrated by fluorescence. |
There has been some evidence that the
GroES is secreted in macrophages during infection. Moreover, it has also been
implicated as one of the major factos in bone resorption in Pott’s disease
(Tuberculosis of the spine). This observation is intriguing since its
function as a co-chaperone essentially limits it to the cytoplasmic location.
Crystal structure of the protein determined in our laboratory revealed
accumulation of negatively charged residues at the top of thedome-like
structure, and thereby suggested putative-metal binding site. This was further confirmed by fluorescence
experiments, which revealed that GroES effectively binds divalent
cations. The binding by divalent
cations brings about profound changes in the conformation of the protein and
induces correlated dynamic motion among different regions of the protein. |
Cation binding
induces conformational changes in the protein, with correlated motions
observed in distant loops as probed by molecular dynamics. |
|
The crystal
structure of M. tuberculosis Hsp65
(GroEL-2 or Cpn60.2) |
Studies on the
GroEL proteins in our laboratory revealed that these proteins unusually exist
in lower oligomeric forms. Since, oligomerization is essential for the
functioning of GroEL, our observations suggest that the M. tuberculosis GroELs may have evolved a promiscuous function.
We are currently attempting studies to decipher the biochemical function of
GroELs in M. tuberculosis, and
trying to understand the molecular features that are responsible for the loss
of oligomerization. |
The crystal of the
dimeric GroEL-2 revealed a very different quaternary association of molecules
(cyan and yellow) as compared to the E.coli
GroEL (red) |
Related Publications
·
Multiple gene
duplication and rapid evolution in the groEL gene: functional
implications (PDF)
K. Goyal, R. Qamra and S.
C. Mande
J. Mol. Evol. (2006) 63, 781-787.
·
Cation mediated
interplay of loops in Mycobacterium tuberculosis Chaperonin-10 (PDF)
S. Vijaykrishnan, R. Qamra, C.
Verma, R. Sen and S. C. Mande
J. Biomolec. Struct. Dyn. (2006) 23, 365- 376.
·
The unusual chaperonins of Mycobacterium tuberculosis (PDF)
R. Qamra, S. C. Mande, A. R. M. Coates and B. Henderson
Tuberculosis (2005) 85, 385- 394.
·
Crystal Structure of the 65 kDa Heat Shock Protein, Chaperonin 60.2 of Mycobacterium tuberculosis (PDF)
R. Qamra and S. C. Mande
J. Bacteriol. (2004) 186, 8105-8113.
·
Mycobacterium
tuberculosis GroEL homologues unusually exist as
lower oligomers and retain the ability to suppress aggregation of substrate
proteins (PDF)
R.
Qamra, V. Srinivas and S. C. Mande
J.
Mol. Biol. (2004) 342, 605-617
·
Structure of Mycobacterium
tuberculosis chaperonin-10 at 3.5 Å resolution (PDF)
B. Taneja and S. C.
Mande
Acta Crystallogr (2002)
D58, 260-266.
·
Three- dimensional
structure of Mycobacterium tuberculosis chaperonin-10 reveals a
partially stable conformation of its mobile loop (PDF)
B. Taneja and S. C.
Mande
Curr. Sci. (2001) 81, 87- 91.
·
Metal ions
modulate the plastic nature of Mycobacterium tuberculosis chaperonin-10
(PDF)
B. Taneja and S. C.
Mande
Prot. Eng.
(2001) 14, 391- 395.
·
Conserved
structural features and sequence patterns in the GroES fold family (PDF)
B. Taneja and S. C.
Mande.
Prot. Eng. (1999) 12, 815- 818.
·
Structure of the
heat shock protein chaperonin-10 of Mycobacterium leprae
S. C. Mande, V. Mehra, B. R. Bloom and W. G. J.
Hol.
Science (1996) 271, 203-206.
