Mycobacterium tuberculosis has Two Chaperonin 60 Proteins

The major perceived function of the bacterial chaperonin 60 protein is to fold cytoplasmic proteins. The finding that many bacterial genera have more than one gene encoding chaperonin 60 proteins is therefore unexpected (Lund 2009). The mycobacteria were among the first bacteria to be shown to express two separate chaperonin 60 proteins. These were the well-studied HSP65 protein, which was renamed chaperonin 60.2, and a second gene encoding a protein termed chaperonin 60.1, which was found to be in an operon with the co-chaperone chaperonin 10 (Kong et al. 1993). This operon structure is the normal finding in most organisms (Lund 2009) and led to the conclusion that chaperonin 60.1 was the major cell stress protein in M. tuberculosis (Kong et al. 1993). However, as will be seen, this hypothesis was incorrect.

As described, the prototypic chaperonin 60 protein is the E. coli protein GroEL, which forms a tetradecameric oligomeric structure (Saibil et al. 2013). However, both M. tuberculosis chaperonin 60 proteins failed to show this oligomeric structure (Qamra et al. 2004; Tormay et al. 2005) and even the crystal structure of the chaperonin 60.2 protein is a dimer (Qamra and Mande 2004). In addition, the ATPase activity of both chaperonin 60 proteins was very low (Qamra et al. 2004;

Tormay et al. 2005). Surprisingly, given these findings, the gene encoding chaperonin 60.2 could replace the groEL gene (in E. coli). In contrast, the gene encoding the chaperonin 60.1 protein was unable to generate viable bacteria, suggesting this protein had lost its protein-folding activity (Hu et al. 2008). This suggested that the M. tuberculosis chaperonin 60.2 protein could form appropriate oligomeric structures within the E. coli cytoplasm. It has been shown that oligomerization of the Cpn60.2 proteins of the mycobacteria can be induced in the presence of kosmotropes (compounds which, unlike chaotropes, stabilize protein structure) or ADP or ATP (Fan et al. 2012). It is unclear what kosmotropes promote the intracellular stabilization of mycobacterial chaperonin 60.2 proteins. In addition, it is not clear how the oligomeric state of these proteins influences their moonlighting behavior.

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