Co-chaperones are proteins that assist
chaperones in
protein folding
Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...
and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by
Hsp70 and
Hsp90
Hsp90 (heat shock protein 90) is a chaperone (protein), chaperone protein that assists other proteins to protein folding, fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of ...
. They are particularly essential in stimulation of the ATPase activity of these chaperone proteins. There are a great number of different co-chaperones however based on their domain structure most of them fall into two groups: J-domain proteins and tetratricopeptide repeats (TPR).
Co-chaperones assist heat shock proteins in the protein folding process. These co-chaperones can function in a number of ways. Primarily co-chaperones are involved in the ATPase functionality of their associated heat shock proteins. Co-chaperones catalyze the hydrolysis ATP to ADP on their respective chaperones which then allows them undergo a large conformational change that allows them to either bind to their substrates with higher affinity or aid in the release of the substrate following protein folding, as in the case of co-chaperone p23.
J-proteins,
DnaJ or Hsp40 are important co-chaperones for Hsp70 and have the ability to bind to polypeptides and then recruit chaperone protein DnaK and passes the polypeptide along to this chaperone by catalyzing ATP hydrolysis that allows DnaK to bind to the unfolded polypeptide with high affinity. Another co-chaperone, GrpE, comes in following the folding of this protein to cause a conformational change in DnaK that allows it to release the folded protein. The mechanism of TPR proteins is less studied these domains have been shown to interact with Hsp90 and Hsp70 and may be involved in the creation of an Hsp70-Hsp90 multi-chaperone complex.
Co-chaperones may also play an important role in misfolding diseases such as cystic fibrosis. An interaction between Hsp90 and its co-chaperone, Aha1, is essential to the proper folding of cystic fibrosis transmembrane conductance regulator (CFTR). Other examples of co-chaperone's role in illness include neurodegenerative diseases. Alzheimer’s and Parkinson’s disease have a number of proteins that can aggregate if not properly chaperoned. Co-chaperones CSPα (DNAJC5), auxilin (DNAJC6) and RME-8 (DNAJC13) are important for preserving folding and assembly, therefore preventing protein aggregation. Detection of mutations in these proteins have been associated with the early onset of neurodegenerative diseases.
List of co-chaperones
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Aha1
Activator of 90 kDa heat shock protein ATPase homolog 1 is an enzyme that in humans is encoded by the ''AHSA1'' gene.
Interactions
AHSA1 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1
Heat shock prote ...
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auxilin
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BAG1
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CAIR-1/Bag-3
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CDC37
Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the ''CDC37'' gene. This protein is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a HSP90 Co-chaperone with spec ...
/p50
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Chp1
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Cysteine string protein (CSP)
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Cyp40
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Djp1
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DnaJ
* E3/E4-
ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
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FKBP4
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GAK
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GroES
Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a protein that in humans is encoded by the ''HSPE1'' gene. The homolog in ''Escherichia coli, E. coli'' is GroES that is a chaperonin ...
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GrpE
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Hch1
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Hip (Hsc70-interacting protein)/ST13
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Hop (Hsp70/Hsp90 organizing protein)/STIP1
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Mrj
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PP5
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Sacsin
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SGT
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Snl1
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SODD/Bag-4
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Swa2/Aux1
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Tom34
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Tom70
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UNC-45
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WISp39
See also
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Chaperone (protein)
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assi ...
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Heat shock protein
Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including ex ...
References
Further reading
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