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An Error has occurred retrieving Wikidata item for infobox GroEL is a protein which belongs to the chaperonin family of molecular chaperones, and is found in many bacteria.[1] It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein complex GroES. In eukaryotes the proteins Hsp60 and Hsp10 are structurally and functionally nearly identical to GroEL and GroES, respectively.


Within the cell, the process of GroEL/ES mediated protein folding involves multiple rounds of binding, encapsulation, and release of substrate protein. Unfolded substrate proteins bind to a hydrophobic binding patch on the interior rim of the open cavity of GroEL, forming a binary complex with the chaperonin. Binding of substrate protein in this manner, in addition to binding of ATP, induces a conformational change that allows association of the binary complex with a separate lid structure, GroES. Binding of GroES to the open cavity of the chaperonin induces the individual subunits of the chaperonin to rotate such that the hydrophobic substrate binding site is removed from the interior of the cavity, causing the substrate protein to be ejected from the rim into the now largely hydrophilic chamber. The hydrophilic environment of the chamber favors the burying of hydrophobic residues of the substrate, inducing substrate folding. Hydrolysis of ATP and binding of a new substrate protein to the opposite cavity sends an allosteric signal causing GroES and the encapsulated protein to be released into the cytosol. A given protein will undergo multiple rounds of folding, returning each time to its original unfolded state, until the native conformation or an intermediate structure committed to reaching the native state is achieved. Alternatively, the substrate may succumb to a competing reaction, such as misfolding and aggregation with other misfolded proteins.[2]


The constricted nature of the interior of the molecular complex strongly favors compact molecular conformations of the substrate protein. Free in solution, long-range, non-polar interactions can only occur at a high cost in entropy. In the close quarters of the GroEL complex, the relative loss of entropy is much smaller. The method of capture also tends to concentrate the non-polar binding sites separately from the polar sites. When the GroEL non-polar surfaces are removed, the chance that any given non-polar group will encounter a non-polar intramolecular site are much greater than in bulk solution. The hydrophobic sites which were on the outside are gathered together at the top of the cis domain and bind each other. The geometry of GroEL requires that the polar structures lead, and they envelop the non-polar core as it emerges from the trans side.


Structurally, GroEL is a dual-ringed tetradecamer, with both the cis and trans rings consisting of seven subunits each. The conformational changes that occur within the central cavity of GroEL cause for the inside of GroEL to become hydrophilic, rather than hydrophobic, and is likely what facilitates protein folding.

The key to the activity of GroEL is in the structure of the monomer. The Hsp60 monomer has three distinct sections separated by two hinge regions. The apical section contains many hydrophobic binding sites for unfolded protein substrates. Many globular proteins won't bind to the apical domain because their hydrophobic parts are clustered inside, away from the aqueous medium since this is the thermodynamically optimal conformation. Thus, these "substrate sites" will only bind to proteins which are not optimally folded. The apical domain also has binding sites for the Hsp10 monomers of GroES.

The equatorial domain has a slot near the hinge point for binding ATP, as well as two attachment points for the other half of the GroEL molecule. The rest of the equatorial section is moderately hydrophilic.

The addition of ATP and GroES has a drastic effect on the conformation of the cis domain. This effect is caused by flexion and rotation at the two hinge points on the Hsp60 monomers. The intermediate domain folds down and inward about 25° on the lower hinge. This effect, multiplied through the cooperative flexing of all monomers, increases the equatorial diameter of the GroEL cage. But the apical domain rotates a full 60° up and out on the upper hinge, and also rotates 90° around the hinge axis. This motion opens the cage very widely at the top of the cis domain, but completely removes the substrate binding sites from the inside of the cage.


GroEL has been shown to interact with GroES,[3][4] ALDH2,[4] Caspase 3[3][5] and Dihydrofolate reductase.[6]

See also


  1. "The universally conserved GroE (Hsp60) chaperonins". Annu. Rev. Microbiol. 45: 301–25. 1991. doi:10.1146/annurev.mi.45.100191.001505. PMID 1683763. 
  2. "Two families of chaperonin: physiology and mechanism". Annu. Rev. Cell Dev. Biol. 23: 115–45. 2007. doi:10.1146/annurev.cellbio.23.090506.123555. PMID 17489689. 
  3. 3.0 3.1 "Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells". EMBO J. 18 (8): 2040–8. Apr 1999. doi:10.1093/emboj/18.8.2040. PMID 10205158. 
  4. 4.0 4.1 "Chaperonin GroESL mediates the protein folding of human liver mitochondrial aldehyde dehydrogenase in Escherichia coli". Biochem. Biophys. Res. Commun. 298 (2): 216–24. Oct 2002. doi:10.1016/S0006-291X(02)02423-3. PMID 12387818. 
  5. "Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis". EMBO J. 18 (8): 2049–56. Apr 1999. doi:10.1093/emboj/18.8.2049. PMID 10205159. 
  6. "Protein folding in the central cavity of the GroEL-GroES chaperonin complex". Nature 379 (6564): 420–6. Feb 1996. doi:10.1038/379420a0. PMID 8559246. 

Further reading

External links