InterPro domain: IPR001844

The assembly of proteins has been thought to be the sole result of properties inherent in the primary sequence of polypeptides themselves. In some cases, however, structural information from other protein molecules is required for correct folding and subsequent assembly into oligomers [ 1 ]. These `helper' molecules are referred to as molecular chaperones, a subfamily of which are the chaperonins [ 2 ]. They are required for normal cell growth (as demonstrated by the fact that no temperature sensitive mutants for the chaperonin genes can be found in the temperature range 20 to 43 degrees centigrade [ 3 ]), and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions [ 3 ]. Type I chaperonins present in eubacteria, mitochondria and chloroplasts require the concerted action of 2 proteins, chaperonin 60 (cpn60) and chaperonin 10 (cpn10). Type II chaperonins, found in eukaryotic cytosol and in Archaebacteria, comprise only a cpn60 member.

The 10kDa chaperonin (cpn10 - or groES in bacteria) exists as a ring-shaped oligomer of between 6 to 8 identical subunits, whereas the 60kDa chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits [ 3 ]. These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The central cavity of the cylindrical cpn60 tetradecamer provides as isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg ²⁺ -ATP dependent manner [ 3 , 4 ]. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.

The 60kDa form of chaperonin is the immunodominant antigen of patients with Legionnaire's disease [ 4 ], and is thought to play a role in the protection of the Legionella spp. bacteria from oxygen radicals within macrophages. This hypothesis is based on the finding that the cpn60 gene is upregulated in response to hydrogen peroxide, a source of oxygen radicals. Cpn60 has also been found to display strong antigenicity in many bacterial species [ 5 ], and has the potential for inducing immune protection against unrelated bacterial infections. The RuBisCO subunit binding protein (which has been implicated in the assembly of RuBisCO) and cpn60 have been found to be evolutionary homologues, the RuBisCO subunit binding protein having the C-terminal Gly-Gly-Met repeat found in all bacterial cpn60 sequences. Although the precise function of this repeat is unknown, it is thought to be important as it is also found in 70kDa heat-shock proteins [ 6 ]. The crystal structure of Escherichia coli GroEL has been resolved to 2.8A [ 6 ].

1. Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature 333, 330-4
2. cDNA clones encoding Arabidopsis thaliana and Zea mays mitochondrial chaperonin HSP60 and gene expression during seed germination and heat shock. Plant Mol. Biol. 18, 873-85
3. Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon from Bacillus subtilis. J. Bacteriol. 174, 3993-9
4. Sequence analysis of the Legionella micdadei groELS operon. FEMS Microbiol. Lett. 61, 31-8
5. Cloning and nucleotide sequence of the Brucella abortus groE operon. Biochim. Biophys. Acta 1130, 120-2
6. The crystal structure of the bacterial chaperonin GroEL at 2.8 A. Nature 371, 578-86