<i>Mycobacterium tuberculosis</i> ClpC1

Kar, Narayani P.; Sikriwal, Deepa; Rath, Parthasarathi; Choudhary, Rakesh Kumar; Batra, Janendra K.

doi:10.1111/j.1742-4658.2008.06738.x

Cited by 42 publications

(45 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conserved autocleavage site between residues 24 (Gly) and 25 (Ser) in the aspartate decarboxylase domain is indicated. (B) Domain organization of ClpC1 is shown as described in ref (35). Within the N-terminal domain, two repeats are labeled I and II.…”

Section: Resultsmentioning

confidence: 99%

“…10 M. tuberculosis ClpC1 works together with the ClpP1 and ClpP2 proteins of the caseinolytic protease complex and displays unfoldase and ATPase activities. 35,36 The Clp protease complex is crucial for viability of M. tuberculosis both in vitro and in vivo, 37,38 whereas the clpC1 gene on its own has been demonstrated to be essential for growth in vitro 31 and within macrophages. 39 Thus, drugs targeting the Clp protease machinery are considered attractive.…”

Section: Discussion and Conclusionmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1

et al. 2017

View full text Add to dashboard Cite

Through mutant selection on agar containing pyrazinoic acid (POA), the bioactive form of the prodrug pyrazinamide (PZA), we recently showed that missense mutations in the aspartate decarboxylase PanD and the unfoldase ClpC1, and loss-of-function mutation of polyketide synthases Mas and PpsA-E involved in phthiocerol dimycocerosate synthesis, cause resistance to POA and PZA in Mycobacterium tuberculosis. Here we first asked whether these in vitro-selected POA/PZA-resistant mutants are attenuated in vivo, to potentially explain the lack of evidence of these mutations among PZA-resistant clinical isolates. Infection of mice with panD, clpC1, and mas/ppsA-E mutants showed that whereas growth of clpC1 and mas/ppsA-E mutants was attenuated, the panD mutant grew as well as the wild-type. To determine whether these resistance mechanisms can emerge within the host, mice infected with wild-type M. tuberculosis were treated with POA, and POA-resistant colonies were confirmed for PZA and POA resistance. Genome sequencing revealed that 82 and 18% of the strains contained missense mutations in panD and clpC1, respectively. Consistent with their lower fitness and POA resistance level, independent mas/ppsA-E mutants were not found. In conclusion, we show that the POA/PZA resistance mechanisms due to panD and clpC1 missense mutations are recapitulated in vivo. Whereas the representative clpC1 mutant was attenuated for growth in the mouse infection model, providing a possible explanation for their absence among clinical isolates, the growth kinetics of the representative panD mutant was unaffected. Why POA/PZA resistance-conferring panD mutations are observed in POA-treated mice but not yet among clinical strains isolated from PZA-treated patients remains to be determined.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussion and Conclusionmentioning

confidence: 99%

In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Earlier, we have shown M. tuberculosis ClpC1 to manifest chaperonic activity in vitro in the absence of any adaptor protein [18]. M. tuberculosis ClpC1 has been shown to interact with RseA, an anti sigma factor, and ClpC1P2 complex has been shown to proteolytically cleave RseA in vitro [19].…”

Section: Introductionmentioning

confidence: 86%

“…The M. tuberculosis H37Rv ClpC1 is an ATP-dependent molecular chaperone which belongs to the class I of Hsp100 family of AAA+ proteins [18]. Earlier, we have shown M. tuberculosis ClpC1 to manifest chaperonic activity in vitro in the absence of any adaptor protein [18].…”

Section: Introductionmentioning

confidence: 99%

The C-Terminus of ClpC1 of Mycobacterium tuberculosis Is Crucial for Its Oligomerization and Function

Bajaj

Batra

2012

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Mycobacterium tuberculosis ClpC1 is a member of the Hsp100/Clp AAA+ family of ATPases. The primary sequence of ClpC1 contains two N-terminal domains and two nucleotide binding domains (NBD). The second NBD has a long C-terminal sub-domain containing several motifs important for substrate interaction. Generally, ClpC proteins are highly conserved, however presence of C-terminal domains of variable lengths is a remarkable difference in ClpC from different species. In this study, we constructed deletion mutants at the C-terminus of M. tuberculosis ClpC1 to determine its role in the structure and function of the protein. In addition, a deletion mutant having the two conserved N-terminal domains deleted was also constructed to investigate the role of these domains in M. tuberculosis ClpC1 function. The N-terminal domains were found to be dispensable for the formation of oligomeric structure, and ATPase and chaperone activities. However, deletions beyond a specific region in the C-terminus of the ClpC1 resulted in oligomerization defects and loss of chaperonic activity of the protein without affecting its ATPase activity. The truncated mutants, defective in oligomerization were also found to have lost the chaperonic activity, showing the formation of oligomer to be required for the chaperonic activity of M. tuberculosis ClpC1. The current study has identified a region in the C-terminus of M. tuberculosis ClpC1 which is essential for its oligomerization and in turn its function.

show abstract

“…We chose E. coli as a host for the recombinant expression of AtClpC1, AtClpC2, and AtClpD. This host was successfully used for the expression of SyClpC (37), ClpC1 from Mycobacterium tuberculosis (MtClpC1) (38) and many others from bacterial origin. AtClpC1 could not be detected under any condition tested.…”

Section: Discussionmentioning

confidence: 99%

Insights into the CLP/HSP100 Chaperone System from Chloroplasts of Arabidopsis thaliana

Rosano¹,

Bruch²,

Ceccarelli

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

HSP100 proteins are molecular chaperones involved in protein quality control. They assist in protein (un)folding, prevent aggregation, and are thought to participate in precursor translocation across membranes. Caseinolytic proteins ClpC and ClpD from plant chloroplasts belong to the HSP100 family. Their role has hitherto been investigated by means of physiological studies and reverse genetics. In the present work, we employed an in vitro approach to delve into the structural and functional characteristics of ClpC2 and ClpD from Arabidopsis thaliana (AtClpC2 and AtClpD). They were expressed in Escherichia coli and purified to near-homogeneity. The proteins were detected mainly as dimers in solution, and, upon addition of ATP, the formation of hexamers was observed. Both proteins exhibited basal ATPase activity (K m , 1.42 mM, V max , 0.62 nmol/ (min ؋ g) for AtClpC2 and K m ϳ19.80 mM, V max ϳ0.19 nmol/ (min ؋ g) for AtClpD). They were able to reactivate the activity of heat-denatured luciferase (ϳ40% for AtClpC2 and ϳ20% for AtClpD). The Clp proteins tightly bound a fusion protein containing a model transit peptide. This interaction was detected by binding assays, where the chaperones were selectively trapped by the transit peptide-containing fusion, immobilized on glutathione-agarose beads. Association of HSP100 proteins to import complexes with a bound transit peptide-containing fusion was also observed in intact chloroplasts. The presented data are useful to understand protein quality control and protein import into chloroplasts in plants.

show abstract

Mycobacterium tuberculosis ClpC1

Cited by 42 publications

References 36 publications

In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1

In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1

The C-Terminus of ClpC1 of Mycobacterium tuberculosis Is Crucial for Its Oligomerization and Function

Insights into the CLP/HSP100 Chaperone System from Chloroplasts of Arabidopsis thaliana

Contact Info

Product

Resources

About