Mycobacterium tuberculosis Chaperonin 60 Proteins, Macrophage Function, and Granuloma Formation
Chaperonin (Cpn) 60, also known as heat-shock protein (HSP) 60 and, in the new nomenclature, HSPD1, is a bacterial molecular chaperone which is found within the bacterial cytoplasm and, in eukaryotic cells, within the mitochondria and chloroplast (Saibil etal. 2013). This gene family is only found in a small number of the Archaea (Macario et al. 2004). Chaperonin 60, as exemplified by the prototypic E. coli protein GroEL, has evolved as a folding machine for a variety of cytosolic proteins. To this end, evolution has crafted an oligomeric structure composed of two seven-membered rings (of 60 kDa subunits) stacked back-to-back, generating two cavities lined with a hydrophobic surface which can bind unfolded polypeptide chains. Once bound, the chaperonin 60 protein undergoes significant molecular movement, which forces the unfolded protein to be ejected from the walls of the cavity into the chamber, which is hydrophilic and favors correct folding (Saibil et al. 2013). It is surprising that this family of intricate protein-folding oligomeric machines also exhibit a bewildering variety of moonlighting actions (Henderson et al. 2013).
In addition to functioning as a molecular chaperone, and having multiple moonlighting actions, chaperonin 60 proteins from microbial pathogens are well-recognized antigenic proteins capable of generating cross-reactive immunity, which is associated with autoimmune disease (van Eden et al. 2005). The relationship between protein moonlighting and auto-antigenicity is described in Chapter 4. The significant immunity to the chaperonin 60.2 (HSP65) protein of M. tuberculosis in patients with tuberculosis has suggested that this protein could be a vaccine candidate (Doimo et al. 2014).