Summary: A family of multisubunit protein complexes that form into large cylindrical structures which bind to and encapsulate non-native proteins. Chaperonins utilize the energy of ATP hydrolysis to enhance the efficiency of PROTEIN FOLDING reactions and thereby help proteins reach their functional conformation. The family of chaperonins is split into GROUP I CHAPERONINS, and GROUP II CHAPERONINS, with each group having its own repertoire of protein subunits and subcellular preferences.

Top Publications

  1. Tortoli E, Mariottini A, Mazzarelli G. Mycobacterium sherrisii isolation from a patient with pulmonary disease. Diagn Microbiol Infect Dis. 2007;57:221-3 pubmed
    ..One of our strains was responsible for pulmonary disease in a middle-aged non-HIV patient; thus, confirming the potential pathogenicity of this species previously reported only in an HIV-positive patient. ..
  2. Dekker C, Stirling P, McCormack E, Filmore H, Paul A, Brost R, et al. The interaction network of the chaperonin CCT. EMBO J. 2008;27:1827-39 pubmed publisher
    ..Our results therefore provide a rich framework for understanding the function of CCT in several essential cellular processes, including epigenetics and cell division. ..
  3. Retzlaff M, Hagn F, Mitschke L, Hessling M, Gugel F, Kessler H, et al. Asymmetric activation of the hsp90 dimer by its cochaperone aha1. Mol Cell. 2010;37:344-54 pubmed publisher
    ..This seems to functionalize the two subunits of the Hsp90 dimer in different ways, in that one subunit can be used for conformational ATPase regulation and the other for substrate protein processing. ..
  4. Raineri E, Ribeca P, Serrano L, Maier T. A more precise characterization of chaperonin substrates. Bioinformatics. 2010;26:1685-9 pubmed publisher
    ..We discuss our findings in relation to established mechanisms of protein folding and evolutionary buffering by chaperones. ..
  5. England J, Lucent D, Pande V. Rattling the cage: computational models of chaperonin-mediated protein folding. Curr Opin Struct Biol. 2008;18:163-9 pubmed publisher
    b>Chaperonins are known to maintain the stability of the proteome by facilitating the productive folding of numerous misfolded or aggregation-prone proteins and are thus essential for cell viability...
  6. Tam S, Geller R, Spiess C, Frydman J. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nat Cell Biol. 2006;8:1155-62 pubmed
    ..Based on the specificity of the Htt-CCT1 interaction, the CCT1 substrate-binding domain may provide a versatile scaffold for therapeutic inhibitors of neurodegenerative disease. ..
  7. Fan M, Rao T, Zacco E, Ahmed M, Shukla A, Ojha A, et al. The unusual mycobacterial chaperonins: evidence for in vivo oligomerization and specialization of function. Mol Microbiol. 2012;85:934-44 pubmed publisher
    The pathogen Mycobacterium tuberculosis expresses two chaperonins, one (Cpn60.1) dispensable and one (Cpn60.2) essential...
  8. Sampaio J, Junior D, de Freitas D, Hofling Lima A, Miyashiro K, Alberto F, et al. An outbreak of keratitis caused by Mycobacterium immunogenum. J Clin Microbiol. 2006;44:3201-7 pubmed
    ..This is the first report of an outbreak where this species was isolated from infected tissues. ..
  9. Cappello F, Conway de Macario E, Marasa L, Zummo G, Macario A. Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy. Cancer Biol Ther. 2008;7:801-9 pubmed

Scientific Experts

More Information


  1. Kitamura A, Kubota H, Pack C, Matsumoto G, Hirayama S, Takahashi Y, et al. Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat Cell Biol. 2006;8:1163-70 pubmed
    ..These results indicate that CCT has an essential role in protecting against the cytotoxicity of polyQ proteins by affecting the course of aggregation. ..
  2. Large A, Lund P. Archaeal chaperonins. Front Biosci (Landmark Ed). 2009;14:1304-24 pubmed
    b>Chaperonins are ubiquitous and essential protein folding machines...
  3. Hawle P, Siepmann M, Harst A, Siderius M, Reusch H, Obermann W. The middle domain of Hsp90 acts as a discriminator between different types of client proteins. Mol Cell Biol. 2006;26:8385-95 pubmed
    ..Thus, Hsp90M seems to discriminate between different substrate types and to adjust the molecular chaperone for proper substrate activation. ..
  4. Spiess C, Miller E, McClellan A, Frydman J. Identification of the TRiC/CCT substrate binding sites uncovers the function of subunit diversity in eukaryotic chaperonins. Mol Cell. 2006;24:25-37 pubmed
    ..localizes to a helical region in the apical domains that is structurally equivalent to that of bacterial chaperonins. Transferring the distal portion of helix 11 between TRiC subunits suffices to transfer specificity for a given ..
  5. Mallam A, Jackson S. Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins. Nat Chem Biol. 2011;8:147-53 pubmed publisher
    ..These results explain how knotted protein structures have withstood evolutionary pressures despite their topological complexity. ..
  6. Stoetzel C, Muller J, Laurier V, Davis E, Zaghloul N, Vicaire S, et al. Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. Am J Hum Genet. 2007;80:1-11 pubmed
  7. Mollapour M, Tsutsumi S, Truman A, Xu W, Vaughan C, Beebe K, et al. Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity. Mol Cell. 2011;41:672-81 pubmed publisher
    ..Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants. ..
  8. Fujiwara S, Aki R, Yoshida M, Higashibata H, Imanaka T, Fukuda W. Expression profiles and physiological roles of two types of molecular chaperonins from the hyperthermophilic archaeon Thermococcus kodakarensis. Appl Environ Microbiol. 2008;74:7306-12 pubmed publisher
    Thermococcus kodakarensis possesses two chaperonins, CpkA and CpkB, and their expression is induced by the downshift and upshift, respectively, of the cell cultivation temperature...
  9. Tokuriki N, Tawfik D. Chaperonin overexpression promotes genetic variation and enzyme evolution. Nature. 2009;459:668-73 pubmed publisher
    ..We examined the ability of the Escherichia coli GroEL/GroES chaperonins to buffer destabilizing and adaptive mutations...
  10. Yu Y, Hamza A, Zhang T, Gu M, Zou P, Newman B, et al. Withaferin A targets heat shock protein 90 in pancreatic cancer cells. Biochem Pharmacol. 2010;79:542-51 pubmed publisher
  11. Williams T, Fares M. The effect of chaperonin buffering on protein evolution. Genome Biol Evol. 2010;2:609-19 pubmed publisher
    ..fate of GroEL clients in the Mycoplasmas, a group of bacteria containing the only known organisms that lack chaperonins. We show that GroEL was lost once in the common ancestor of a monophyletic subgroup of Mycoplasmas, and we ..
  12. Kubota S, Kubota H, Nagata K. Cytosolic chaperonin protects folding intermediates of Gbeta from aggregation by recognizing hydrophobic beta-strands. Proc Natl Acad Sci U S A. 2006;103:8360-5 pubmed
    ..These findings indicate that one of the CCT/TRiC-specific targets is hydrophobic beta-strands, which are highly prone to aggregation. ..
  13. Gray P, Prince T, Cheng J, Stevenson M, Calderwood S. Targeting the oncogene and kinome chaperone CDC37. Nat Rev Cancer. 2008;8:491-5 pubmed publisher
    ..CDC37 is thus a candidate for broad-spectrum molecular cancer therapy. ..
  14. Gray P, Stevenson M, Calderwood S. Targeting Cdc37 inhibits multiple signaling pathways and induces growth arrest in prostate cancer cells. Cancer Res. 2007;67:11942-50 pubmed
    ..Thus, Cdc37 is essential for maintaining prostate tumor cell growth and may represent a novel target in the search for multitargeted therapies based on the HSP90 chaperone system. ..
  15. Jewett A, Shea J. Do chaperonins boost protein yields by accelerating folding or preventing aggregation?. Biophys J. 2008;94:2987-93 pubmed publisher
  16. Lund P. Multiple chaperonins in bacteria--why so many?. FEMS Microbiol Rev. 2009;33:785-800 pubmed publisher
    A significant proportion of bacteria express two or more chaperonin genes. Chaperonins are a group of molecular chaperones, defined by sequence similarity, required for the folding of some cellular proteins...
  17. Jacob E, Horovitz A, Unger R. Different mechanistic requirements for prokaryotic and eukaryotic chaperonins: a lattice study. Bioinformatics. 2007;23:i240-8 pubmed
    ..All chaperonins have a ring structure with a cavity in which the substrate protein folds...
  18. Kabir M, Sherman F. Overexpressed ribosomal proteins suppress defective chaperonins in Saccharomyces cerevisiae. FEMS Yeast Res. 2008;8:1236-44 pubmed publisher
    ..We suggest that certain overexpressed ribosomal and other proteins can act as weak chaperones, phenotypically alleviating the partial defects of mutationally altered Cct subunits. ..
  19. Turenne C, Wallace R, Behr M. Mycobacterium avium in the postgenomic era. Clin Microbiol Rev. 2007;20:205-29 pubmed
    ..avium subsets in isolation, it is expected that attention to the similarities and differences between M. avium organisms will provide greater insight into their fundamental differences, including their propensity to cause disease...
  20. Lucent D, England J, Pande V. Inside the chaperonin toolbox: theoretical and computational models for chaperonin mechanism. Phys Biol. 2009;6:015003 pubmed publisher
    Despite their immense importance to cellular function, the precise mechanism by which chaperonins aid in the folding of other proteins remains unknown...
  21. Smith J, Clarke P, de Billy E, Workman P. Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors. Oncogene. 2009;28:157-69 pubmed publisher
    ..These results support an essential role for CDC37 in concert with HSP90 in maintaining oncogenic protein kinase clients and endorse the therapeutic potential of targeting CDC37 in cancer. ..
  22. Vaughan C, Gohlke U, Sobott F, Good V, Ali M, Prodromou C, et al. Structure of an Hsp90-Cdc37-Cdk4 complex. Mol Cell. 2006;23:697-707 pubmed
    ..Comparison with the crystal structure of Hsp90 allows us to identify the locations of Cdc37 and Cdk4 in the complex and suggests a mechanism by which conformational changes in the kinase are coupled to the Hsp90 ATPase cycle...
  23. Yam A, Xia Y, Lin H, Burlingame A, Gerstein M, Frydman J. Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. Nat Struct Mol Biol. 2008;15:1255-62 pubmed publisher
    ..Thus, TRiC may have evolved to protect complex protein topologies within its central cavity during biosynthesis and folding. ..
  24. Marion V, Stoetzel C, Schlicht D, Messaddeq N, Koch M, Flori E, et al. Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc Natl Acad Sci U S A. 2009;106:1820-5 pubmed publisher
    ..This strongly suggests that a peripheral primary dysfunction of adipogenesis participates to the pathogenesis of obesity in BBS. ..
  25. Zebol J, Hewitt N, Moretti P, Lynn H, Lake J, Li P, et al. The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1. Int J Biochem Cell Biol. 2009;41:822-7 pubmed publisher
    ..Thus, combined this data suggests that SK1 is a CCT/TRiC substrate, and that this chaperonin facilitates folding of newly translated SK1 into its mature active form. ..
  26. Smith J, Workman P. Targeting CDC37: an alternative, kinase-directed strategy for disruption of oncogenic chaperoning. Cell Cycle. 2009;8:362-72 pubmed
    ..Here we discuss the therapeutic possibilities of targeting CDC37 for cancer treatment in light of recent significant findings. ..
  27. Booth C, Meyer A, Cong Y, Topf M, Sali A, Ludtke S, et al. Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT. Nat Struct Mol Biol. 2008;15:746-53 pubmed publisher
    All chaperonins mediate ATP-dependent polypeptide folding by confining substrates within a central chamber...
  28. Techtmann S, Robb F. Archaeal-like chaperonins in bacteria. Proc Natl Acad Sci U S A. 2010;107:20269-74 pubmed publisher
    b>Chaperonins (CPN) are ubiquitous oligomeric protein machines that mediate the ATP-dependent folding of polypeptide chains...
  29. Caplan A, Mandal A, Theodoraki M. Molecular chaperones and protein kinase quality control. Trends Cell Biol. 2007;17:87-92 pubmed
    ..This requirement might relate to conformational changes that take place during the protein kinase activity cycle. ..
  30. Clarke A. Cytosolic chaperonins: a question of promiscuity. Mol Cell. 2006;24:165-7 pubmed
    b>Chaperonins in the eukaryotic cytosol are more mysterious than their bacterial counterparts, with a heterogeneity of protein binding surfaces...
  31. Bigotti M, Bellamy S, Clarke A. The asymmetric ATPase cycle of the thermosome: elucidation of the binding, hydrolysis and product-release steps. J Mol Biol. 2006;362:835-43 pubmed
    ..These data highlight the importance of the highly populated thermosome/ADP/Pi complex in the molecular mechanism. ..
  32. Pappenberger G, McCormack E, Willison K. Quantitative actin folding reactions using yeast CCT purified via an internal tag in the CCT3/gamma subunit. J Mol Biol. 2006;360:484-96 pubmed
    ..In this pure in vitro system, the human beta-actin mutants, D244S and G150P, show impaired folding behaviour in the manner predicted by our sequence-specific recognition model for CCT-actin interaction. ..
  33. Seo S, Baye L, Schulz N, Beck J, Zhang Q, Slusarski D, et al. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010;107:1488-93 pubmed publisher
    ..a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly, which transports vesicles to the cilia...
  34. Xu X, Wang J, Xuan Z, Goldshmidt A, Borrill P, Hariharan N, et al. Chaperonins facilitate KNOTTED1 cell-to-cell trafficking and stem cell function. Science. 2011;333:1141-4 pubmed publisher
    ..Genetic and physical interaction data show a functional relevance for chaperonins in KNOX family-dependent stem cell maintenance...
  35. Carcoforo P, Ura B, Mischiati C, Squerzanti M, Lanzara V, Cervellati C, et al. Comparative proteomic analysis of ductal breast carcinoma demonstrates an altered expression of chaperonins and cytoskeletal proteins. Mol Med Rep. 2013;7:1700-4 pubmed publisher
    ..Samples of normal and cancerous tissue obtained form 28 patients were analyzed. Chaperonins and cytoskeletal proteins predominated among the 11 proteins for which major changes in abundance were ..
  36. Kanzaki T, Iizuka R, Takahashi K, Maki K, Masuda R, Sahlan M, et al. Sequential action of ATP-dependent subunit conformational change and interaction between helical protrusions in the closure of the built-in lid of group II chaperonins. J Biol Chem. 2008;283:34773-84 pubmed publisher
  37. Clare D, Stagg S, Quispe J, Farr G, Horwich A, Saibil H. Multiple states of a nucleotide-bound group 2 chaperonin. Structure. 2008;16:528-34 pubmed publisher
  38. Bigotti M, Clarke A. Chaperonins: The hunt for the Group II mechanism. Arch Biochem Biophys. 2008;474:331-9 pubmed publisher
    b>Chaperonins are multi-subunit complexes that enhance the efficiency of protein-folding reactions by capturing protein substrates in their central cavities...
  39. Fujiwara K, Taguchi H. Filamentous morphology in GroE-depleted Escherichia coli induced by impaired folding of FtsE. J Bacteriol. 2007;189:5860-6 pubmed
    ..Based on these findings, we concluded that FtsE is a target substrate of the GroE system in E. coli cell division...
  40. Okada M, Kita Y, Nakajima T, Kanamaru N, Hashimoto S, Nagasawa T, et al. Evaluation of a novel vaccine (HVJ-liposome/HSP65 DNA+IL-12 DNA) against tuberculosis using the cynomolgus monkey model of TB. Vaccine. 2007;25:2990-3 pubmed
    ..These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis for human clinical trials. ..
  41. Horwich A, Fenton W, Chapman E, Farr G. Two families of chaperonin: physiology and mechanism. Annu Rev Cell Dev Biol. 2007;23:115-45 pubmed
    b>Chaperonins are large ring assemblies that assist protein folding to the native state by binding nonnative proteins in their central cavities and then, upon binding ATP, release the substrate protein into a now-encapsulated cavity to ..
  42. Grantham J, Brackley K, Willison K. Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells. Exp Cell Res. 2006;312:2309-24 pubmed
    ..There are no large-scale effects on cytoplasmic protein synthesis or a general heat shock response during periods of low CCT activity. ..
  43. Behrends C, Langer C, Boteva R, Böttcher U, Stemp M, Schaffar G, et al. Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. Mol Cell. 2006;23:887-97 pubmed
    ..We suggest that TRiC cooperates with the Hsp70 system as a key component in the cellular defense against amyloid-like protein misfolding. ..
  44. Reischl U, Melzl H, Kroppenstedt R, Miethke T, Naumann L, Mariottini A, et al. Mycobacterium monacense sp. nov. Int J Syst Evol Microbiol. 2006;56:2575-8 pubmed
    ..Phylogenetic analysis revealed that these four strains were most closely related to Mycobacterium doricum. The type strain of Mycobacterium monacense sp. nov. is B9-21-178T (=DSM 44395T=CIP 109237T). ..
  45. Kim H, Kim E, Cerny J, Moudgil K. Antibody responses to mycobacterial and self heat shock protein 65 in autoimmune arthritis: epitope specificity and implication in pathogenesis. J Immunol. 2006;177:6634-41 pubmed
    ..These results are of significance in further understanding of the role of humoral immunity in the pathogenesis of autoimmune arthritis. ..
  46. Bonshtien A, Weiss C, Vitlin A, Niv A, Lorimer G, Azem A. Significance of the N-terminal domain for the function of chloroplast cpn20 chaperonin. J Biol Chem. 2007;282:4463-9 pubmed
    b>Chaperonins cpn60 and cpn10 are essential proteins involved in cellular protein folding...
  47. Satpute S, Soukhareva N, Scott D, Moudgil K. Mycobacterial Hsp65-IgG-expressing tolerogenic B cells confer protection against adjuvant-induced arthritis in Lewis rats. Arthritis Rheum. 2007;56:1490-6 pubmed
    ..Mycobacterial Hsp65-IgG-expressing B cells can successfully attenuate the progression of AIA. This study introduces a promising approach for the treatment of arthritis that should be further explored. ..
  48. Sreeramulu S, Jonker H, Langer T, Richter C, Lancaster C, Schwalbe H. The human Cdc37.Hsp90 complex studied by heteronuclear NMR spectroscopy. J Biol Chem. 2009;284:3885-96 pubmed publisher
    ..NMR and mutagenesis experiments reveal Leu-205 in Cdc37 as a key residue enabling complex formation. These findings can be very useful in the development of small molecule inhibitors against cancer. ..
  49. Zhang T, Hamza A, Cao X, Wang B, Yu S, Zhan C, et al. A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. Mol Cancer Ther. 2008;7:162-70 pubmed publisher
    ..The data suggest that celastrol is a novel Hsp90 inhibitor to disrupt Hsp90-Cdc37 interaction against pancreatic cancer cells. ..
  50. Miyata Y. Protein kinase CK2 in health and disease: CK2: the kinase controlling the Hsp90 chaperone machinery. Cell Mol Life Sci. 2009;66:1840-9 pubmed publisher
    ..The tumor kinome appears to become addicted to the Hsp90-Cdc37 chaperone system, thus, targeting Hsp90, Cdc37, and CK2 is a promising strategy for cancer treatment. ..
  51. Reissmann S, Parnot C, Booth C, Chiu W, Frydman J. Essential function of the built-in lid in the allosteric regulation of eukaryotic and archaeal chaperonins. Nat Struct Mol Biol. 2007;14:432-40 pubmed
    b>Chaperonins are allosteric double-ring ATPases that mediate cellular protein folding...
  52. Kim E, Chi H, Bouziane M, Gaur A, Moudgil K. Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-gamma. Clin Immunol. 2008;127:98-106 pubmed publisher
    ..These results provide a novel perspective on the pathogenesis of autoimmune arthritis. ..
  53. Weiss C, Bonshtien A, Farchi Pisanty O, Vitlin A, Azem A. Cpn20: siamese twins of the chaperonin world. Plant Mol Biol. 2009;69:227-38 pubmed publisher
    ..Lastly, we hypothesize as to the oligomeric structure and raison d'être of this unusual co-chaperonin homolog. ..