Santosh C M Kumar

Publications (15) View all

• Chapter: Evolution of Bacterial Chaperonin 60 Paralogues and Moonlighting Activity.

  • Shekhar C. Mande, C M Santosh Kumar, Aditi Sharma
  01/2013: pages 1-41;
• Source

  Available from: Santosh C M Kumar

  Article: Facilitated oligomerization of mycobacterial GroEL: evidence for phosphorylation-mediated oligomerization.

  C M Santosh Kumar, Garima Khare, C V Srikanth, Anil K Tyagi, Abhijit A Sardesai, Shekhar C Mande
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  ABSTRACT: The distinctive feature of the GroES-GroEL chaperonin system in mediating protein folding lies in its ability to exist in a tetradecameric state, form a central cavity, and encapsulate the substrate via the GroES lid. However, recombinant GroELs of Mycobacterium tuberculosis are unable to act as effective molecular chaperones when expressed in Escherichia coli. We demonstrate here that the inability of M. tuberculosis GroEL1 to act as a functional chaperone in E. coli can be alleviated by facilitated oligomerization. The results of directed evolution involving random DNA shuffling of the genes encoding M. tuberculosis GroEL homologues followed by selection for functional entities suggested that the loss of chaperoning ability of the recombinant mycobacterial GroEL1 and GroEL2 in E. coli might be due to their inability to form canonical tetradecamers. This was confirmed by the results of domain-swapping experiments that generated M. tuberculosis-E. coli chimeras bearing mutually exchanged equatorial domains, which revealed that E. coli GroEL loses its chaperonin activity due to alteration of its oligomerization capabilities and vice versa for M. tuberculosis GroEL1. Furthermore, studying the oligomerization status of native GroEL1 from cell lysates of M. tuberculosis revealed that it exists in multiple oligomeric forms, including single-ring and double-ring variants. Immunochemical and mass spectrometric studies of the native M. tuberculosis GroEL1 revealed that the tetradecameric form is phosphorylated on serine-393, while the heptameric form is not, indicating that the switch between the single- and double-ring variants is mediated by phosphorylation.
  Journal of bacteriology 09/2009; 191(21):6525-38. · 3.94 Impact Factor
• Conference Proceeding: Directed Evolution of Functional GroELs From Mycobacterium tuberculosis GroELs: Phenotypic and Sequence Analysis of the Mutants

  C. M. Santosh Kumar, Rohini Qamra, C. V. Srikanth, Abhijit A. Sardesai, Shekhar C. Mande
  Meeting on Molecular Chaperones and Heat Shock Response, Cold Spring Harbour Laboratory, NY; 01/2006
• Source

  Available from: Santosh C M Kumar

  Article: Functional Analysis of M. tuberculosis Chaperones.

  Santosh Kumar C. M
• Source

  Available from: Santosh C M Kumar

  Article: Protein chaperones and non-protein substrates: on substrate promiscuity of GroEL.

  C. M. Santosh Kumar, Shekhar C. Mande
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  ABSTRACT: Chaperonins are a group of molecular chaperones that form large multi subunit structures and are found in all forms of life. Encoded by the groEL and groES genes, bacterial chaperonins are required for appropriate folding of many cellular proteins. A significant number of bacterial species are known to express multiple copies of chaperonin genes, possibly to confer redundancy of GroEL function in these species. It is also likely that the paralogous GroELs might be undergoing diversification of function as a consequence of gene duplication. We argue in this article that different chaperonins in an organism might be involved in distinct biochemical functions that remain to be discovered, some of which might be modulated by different oligomeric states of the chaperonins.
  Current science. 01/2011; 100:1646.