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Structural Biology » Academic Projects |
| 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.
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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. |
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Accumulation of
negatively charged
residues suggested
binding site for divalent
cations, later
demonstrated by
fluorescence. |
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Cation binding induces
conformational changes
in the protein, with
correlated motions
observed in distant loops
as probed by molecular
dynamics. |
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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. |
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The crystal structure of
M. tuberculosis Hsp65
(GroEL-2 or Cpn60.2) |
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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) |
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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.
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The unusual chaperonins of Mycobacterium tuberculosis (PDF)
R. Qamra, S. C. Mande, A. R. M. Coates and B. Henderson
Tuberculosis (2005) 85, 385- 394.
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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.
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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
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Structure of Mycobacterium tuberculosis chaperonin-10 at 3.5 Å resolution (PDF)
B. Taneja and S. C. Mande
Acta Crystallogr (2002) D58, 260-266.
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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.
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Metal ions modulate the plastic nature of Mycobacterium tuberculosis chaperonin-10 (PDF)
B. Taneja and S. C. Mande
Prot. Eng. (2001) 14, 391- 395.
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Conserved structural features and sequence patterns in the GroES fold family (PDF)
B. Taneja and S. C. Mande.
Prot. Eng. (1999) 12, 815- 818.
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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.
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