Mycobacterium tuberculosis GroEL homologues unusually exist as lower oligomers and retain the ability to suppress aggregation of substrate proteins.

Chaperonin-60s are large double ring oligomeric proteins with a central cavity where unfolded polypeptides undergo productive folding. In conjunction with their co-chaperonin, Chaperonin-60s bind non-native polypeptides and facilitate their refolding in an ATP-dependent manner. The ATPase activity of Chaperonin-60 is tightly regulated by the 10 kDa co-chaperonin. In contrast to most other bacterial species, Mycobacterium tuberculosis genome carries a duplicate set of cpn60 genes, one of which occurs on the groESL operon (cpn60.1), while the other is separately arranged on the chromosome (cpn60.2). Biophysical characterization of the mycobacterial proteins showed that these proteins exist as lower oligomers and not tetradecamers, an unexpected property much different from the other known Chaperonin-60s. Failure of the M.tuberculosis chaperonins to oligomerize can be attributed to amino acid mutations at the oligomeric interface. Rates of ATP hydrolysis of the M.tuberculosis chaperonins showed that these proteins possess a very weak ATPase activity. Both the M.tuberculosis chaperonins were partially active in refolding substrate proteins. Interestingly, their refolding activity was seen to be independent of the co-chaperonin and ATP. We hypothesize that the ATP independent chaperones might offer benefit to the pathogen by promoting its existence in the latent phase of its life cycle.