Editing GroEL (section)

== Structure ==
Under normal physiological conditions, HSP60 is a 60 kilodalton oligomer composed of monomers that form a complex arranged as two stacked heptameric rings.<ref name=three>{{cite journal |vauthors=Cheng MY, Hartl FU, Horwich AL |title=The mitochondrial chaperonin hsp60 is required for its own assembly |journal=Nature |volume=348 |issue=6300 |pages=455–8 |date=November 1990 |pmid=1978929 |doi=10.1038/348455a0|bibcode=1990Natur.348..455C |s2cid=28394330 }}</ref> This double ring structure forms a large central cavity in which the unfolded protein binds via [[hydrophobic]] interactions.<ref name=four>{{cite journal  |vauthors=Fenton WA, etal |title=Residues in chaperonin GroEL required for polypeptide binding and release |journal=Nature |volume=371 |issue=6498 |pages=614–9 |date=October 1994 |pmid=7935796 |doi=10.1038/371614a0|bibcode=1994Natur.371..614F |s2cid=23840816 }}</ref> This structure is typically in equilibrium with each of its individual components: monomers, heptamers, and tetradecamers.<ref name=five>{{cite journal  |vauthors=Habich C, etal |title=Heat shock protein 60: regulatory role on innate immune cells |journal=Cell. Mol. Life Sci. |volume=64 |issue=6 |pages=742–51 |date=March 2007 |pmid=17221165 |doi=10.1007/s00018-007-6413-7|s2cid=24067484 |pmc=11138415 }}</ref> Recent studies have begun to suggest that in addition to its typical location in the mitochondria, HSP60 can also be found in the cytoplasm under normal physiological conditions.<ref name=one/>

Each subunit of HSP60 has three [[protein domain|domains]]: the apical domain, the equatorial domain, and the intermediate domain.<ref name=six/> The equatorial domain contains the binding site for [[Adenosine triphosphate|ATP]] and for the other heptameric ring. The intermediate domain binds the equatorial domain and the apical domain together.<ref name=six>{{cite journal  |vauthors=Ranford JC, etal |title=Chaperonins are cell-signalling proteins: the unfolding biology of molecular chaperones |journal=Expert Rev Mol Med |volume=2 |issue=8 |pages=1–17 |date=September 2000 |pmid=14585136 |doi=10.1017/S1462399400002015 |s2cid=38110138 |url=http://journals.cambridge.org/abstract_S1462399400002015|url-access=subscription }}</ref> The intermediate domain induces a conformational change when ATP is bound allowing for an alternation between the [[hydrophilic]] and [[hydrophobic]] substrate binding sites.<ref name=six/> In its inactive state, the protein is in a hydrophobic state. When activated by ATP, the intermediate domain undergoes a conformational change that exposes the hydrophilic region. This insures fidelity in protein binding.<ref name=six/> [[Chaperonin 10]] aids HSP60 in folding by acting as a dome-like cover on the ATP active form of HSP60. This causes the central cavity to enlarge and aids in protein folding.<ref name=six/> See the above figure for further detail on the structure.

[[File:HSP60-1C7.jpg|thumb|A [[monoclonal antibody]] to HSP60 was used to stain human [[HeLa cells]] grown in tissue culture. The antibody reveals cellular mitochondria in red. The blue signal is due to a DNA binding dye which reveals cell nuclei. Antibody staining and image courtesy of [[EnCor Biotechnology]] Inc.]]

[[Image:HSP60 Protein Sequence.jpg|thumb|center|600px|Amino acid and structural sequence of HSP60 Protein.<ref name="pmid10329779">{{PDB|1SRV}}; {{cite journal  |vauthors=Walsh MA, etal | title = Taking MAD to the extreme: ultrafast protein structure determination | journal = Acta Crystallogr. D | volume = 55 | issue = 6 | pages = 1168–73 |date=June 1999 | pmid = 10329779 | doi = 10.1107/S0907444999003698| bibcode = 1999AcCrD..55.1168W }}</ref>]]

The mitochondrial HSP60 [[sequence]] contains a series of G repeats at the [[C-terminal]].<ref name=two/> The structure and function of this sequence is not quite known. The [[N-terminal]] contains a pre-sequence of hydroxylated [[amino acids]], namely [[arginine]], [[lysine]], [[serine]], and [[threonine]], which serve as directors for the importation of the protein into the mitochondria.<ref name=two/>

The predicted structure of HSP60 includes several vertical [[sine waves]], [[alpha helices]], [[beta sheets]], and 90 degree turns. There are regions of [[hydrophobicity]] where the protein presumably spans the [[biological membrane|membrane]]. There are also three N-linked glycosylation sites at positions 104, 230, 436.<ref name=four/> The sequence and secondary structure for the mitochondrial protein are illustrated in the above image obtained from the Protein Data Bank.

Newer information has begun to suggest that the HSP60 found in the mitochondria differs from that of the cytoplasm. With respect to the amino acid sequence, the cytoplasmic HSP60 has an N-terminal sequence not found in the mitochondrial protein.<ref name=one/> In [[gel electrophoresis]] analysis, significant differences were found in the migration of cytoplasmic and mitochondrial HSP60. The cytoplasmic HSP60 contains a [[Signal peptide|signal sequence]] of 26 [[amino acids]] on the N terminus. This sequence is highly degenerate and is capable of folding into [[amphiphilic helix]].<ref name=one/>  [[Antibodies]] against HSP60 targeted both the mitochondrial and cytoplasmic form.<ref name=one/> Nonetheless, antibodies against the signal sequence targeted only the cytoplasmic form.  Under normal physiological condition, both are found in relatively equal concentrations.<ref name=one/>  In times of stress or high need of HSP60 in either the cytoplasm or the mitochondria, the cell is capable for compensating by increasing the presence of HSP60 in one compartment and decreasing its concentration in the opposite compartment.