Mycobacterial chaperonins: the tail wags the dog

Abstract

Molecular chaperones are defined as proteins that assist the noncovalent assembly of other protein-containing structures in vivo, but which are not components of these structures when they are carrying out their normal biological functions. There are numerous families of protein that fit this definition of molecular chaperones, the most ubiquitous of which are the chaperonins and the Hsp70 families, both of which are required for the correct folding of nascent polypeptide chains and thus essential genes for cell viability. The groE genes of Escherichia coli were the first chaperonin genes to be discovered, within an operon comprising two genes, groEL and groES, that function together in the correct folding of nascent polypeptide chains. The identification of multiple groEL genes in mycobacteria, only one of which is operon-encoded with a groES gene, has led to debate about the functions of their encoded proteins, especially as the essential copies are surprisingly often not the operon-encoded genes. Comparisons of these protein sequences reveals a consistent functional homology and identifies an actinomycete-specific chaperonin family, which may chaperone the folding of enzymes involved in mycolic acid synthesis and thus provide a unique target for the development of a new class of broad-spectrum antimycobacterial drugs.

Multiple chaperonins in bacteria—novel functions and non-canonical behaviors

“…While GroEL1 has a His-rich sequence, GroEL2 has a Gly-Met-rich sequence at the C-terminus, homologous to the E. coli counterpart. Thus, probably, GroEL2 is essential and GroEL1 is dispensable (Stewart et al 2002;Colaco and MacDougall 2013). Taken together, GroEL2, being the essential chaperonin and bearing the Cterminus homologous to E. coli GroEL, might be functioning as a general chaperonin for mycobacterium, while GroEL1, being a dispensable chaperonin but involved in critical steps in disease progression such as granuloma and biofilm formation, appears to be involved in folding special class of proteins such as those involved in pathogenicity and perhaps metal-binding proteins, owing to its His-rich C-terminus, via trans mechanism (Chaudhuri et al 2001).…”

“…All the GroEL2 homologues show GGMlike segment, while the GroEL1 and GroEL3 homologues sport histidine-rich and patternless tails, respectively. Interestingly, GroEL2 is indispensable for regular growth, while Hisrich-tail-bearing GroEL1 is dispensable for normal growth but required for pathogenesis (Colaco and MacDougall 2013). Considering that GGM tails interact with substrates in the cavity, it is tempting to speculate that the GGM-bearing GroEL2, which is an essential chaperonin, might be acting as a generalist chaperonin in the cell, while GroEL1 is specialized for folding proteins involved in pathogenesis.…”

Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness

“…26 This is further supported by the fact that only the HSP60.1 isoform contains the C-terminal GGM-repeat motif that is typically found in canonical chaperonin systems. 23,28,31,32 Collectively, these results suggest that T. brucei may be susceptible to HSP60-targeting antibiotics. Targeting the HSP60/10 chaperonins for antibiotic development would be a unique polypharmacological strategy as one drug could potentially inhibit the three chaperonin isoforms and have the cascading effect of modulating hundreds of downstream proteins.…”

Comparison of Actinobacteria communities from human‐impacted and pristine karst caves

“…In the case of Actinobacteria , hsp 65 encodes a molecular chaperone (a 65‐kDa heat‐shock protein), which, when amplified by specific primers (Telenti et al, 1993 ), has been used as a molecular marker to identify a large number of isolates (Rodríguez‐Nava et al, 2006 , 2007 ). A single copy of this gene is present in Actinobacteria genomes, unlike the 16S rRNA gene marker (Colaco & MacDougall, 2014 ). Additionally, the length of the amplified hsp 65 fragment (441 bp) is sufficient for amplicon sequencing.…”