, 1993) As the N-terminal 60 residues, which include the ATP bin

, 1993). As the N-terminal 60 residues, which include the ATP binding site, are undefined in the crystal structure of dimeric Cpn60.2 (Qamra & Mande, 2004), it is likely that the binding of nucleotide may also assist in stabilising the functional oligomers of this chaperonin in vivo (Fan et al., 2012). These results conclusively demonstrate that the mycobacterial Hsp65, or Cpn60.2, is the

structural and functional equivalent of the E. coli GroEL and is responsible for the correct folding of essential housekeeping genes as also suggested by the deletional analysis of mutants of M. smegmatis, M. tuberculosis and M. bovis BCG (Ojha et al., 2005; Hu et al., 2008; Wang et al., 2011). This, however, leaves open the intriguing question of the function of the nonessential Cpn60.1, particularly as the recent structural study of M. tuberculosis Cpn60.1 suggests that it may indeed act as a AZD8055 molecular weight conventional

chaperonin (Sielaff et al., 2011) in marked contrast to earlier gene deletion studies that proposed a more specialised role in aiding biofilm formation and nonplanktonic growth (Ojha et al., 2005; Hu et al., 2008; Wang et al., 2011). A possible resolution of this apparent paradox is if the two cpn genes code for chaperonins that are involved in the folding of two distinct classes of cellular proteins, with Cpn60.1 chaperoning the folding of a class of nonessential proteins. This possibility is supported by a comparison of the two Cpn60 sequences and, in particular, their more divergent Epacadostat price C-terminal domains. The canonical E. coli groEL gene encodes a chaperonin with a C-terminal tail rich in glycine and methionine residues that is also seen in the mycobacterial cpn60.2 sequence, but not Tryptophan synthase in the cpn60.1 gene, which has a distinct histidine-rich C-terminal tail instead (Fig. 1; Kong et al., 1993; Lund, 2001; Lund, 2009). This sequence difference raises the possibility that the C-terminal tail may be characteristic of the functional equivalents of the E. coli GroEL, such as the

mycobacterial Cpn60.2, and suggests that the glycine/methionine tail may be used to identify those chaperonins that mediate the folding of essential housekeeping genes. This suggestion is supported by several studies across a number of bacteria that contain multiple chaperonin genes, where deletion studies have revealed that only one of these genes appears to be essential for viability (Lund, 2001, 2009). In all these, the essential cpn60 genes encode proteins with a glycine- and methionine-rich C-terminal tail (Fig. 1 and C. Colaco, unpublished data). Moreover, it should also be noted that the third Cpn60 sequence found in some mycobacteria, such as M. smegmatis, has a distinct C-terminal tail that is neither glycine-/methionine-rich nor histidine-rich (C. Colaco, unpublished data).

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