1932

Abstract

The chaperonins are ubiquitous and essential nanomachines that assist in protein folding in an ATP-driven manner. They consist of two back-to-back stacked oligomeric rings with cavities in which protein (un)folding can take place in a shielding environment. This review focuses on GroEL from and the eukaryotic chaperonin-containing t-complex polypeptide 1, which differ considerably in their reaction mechanisms despite sharing a similar overall architecture. Although chaperonins feature in many current biochemistry textbooks after being studied intensively for more than three decades, key aspects of their reaction mechanisms remain under debate and are discussed in this review. In particular, it is unclear whether a universal reaction mechanism operates for all substrates and whether it is passive, i.e., aggregation is prevented but the folding pathway is unaltered, or active. It is also unclear how chaperonin clients are distinguished from nonclients and what are the precise roles of the cofactors with which chaperonins interact.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-082521-113418
2022-05-09
2024-04-14
Loading full text...

Full text loading...

/deliver/fulltext/biophys/51/1/annurev-biophys-082521-113418.html?itemId=/content/journals/10.1146/annurev-biophys-082521-113418&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Amit M, Weisberg SJ, Nadler-Holly M, McCormack EA, Feldmesser E et al. 2010. Equivalent mutations in the eight subunits of the chaperonin CCT produce dramatically different cellular and gene expression phenotypes. . J. Mol. Biol. 401:532–43
    [Google Scholar]
  2. 2.
    Ansari MY, Batra SD, Ojha H, Dhiman K, Ganguly A et al. 2020. A novel function of Mycobacterium tuberculosis chaperonin paralog GroEL1 in copper homeostasis. FEBS Lett 594:3305–23
    [Google Scholar]
  3. 3.
    Arranz R, Martín-Benito J, Valpuesta JM 2018. Structure and function of the cochaperone prefoldin. Adv. Exp. Med. Biol. 1106:119–31
    [Google Scholar]
  4. 4.
    Azia A, Unger R, Horovitz A. 2012. What distinguishes GroEL substrates from other Escherichia coli proteins?. FEBS J 279:543–50
    [Google Scholar]
  5. 5.
    Balchin D, Miličić G, Strauss M, Hayer-Hartl M, Hartl FU. 2018. Pathway of actin folding directed by the eukaryotic chaperonin TRiC. Cell 174:1507–21
    [Google Scholar]
  6. 6.
    Bandyopadhyay B, Goldenzweig A, Unger T, Adato O, Fleishman SJ et al. 2017. Local energetic frustration affects the dependence of green fluorescent protein folding on the chaperonin GroEL. J. Biol. Chem. 292:20583–91
    [Google Scholar]
  7. 7.
    Bandyopadhyay B, Mondal T, Unger R, Horovitz A. 2019. Contact order is a determinant for the dependence of GFP folding on the chaperonin GroEL. Biophys. J. 116:42–48
    [Google Scholar]
  8. 8.
    Bergeron LM, Shis DL, Gomez L, Clark DS. 2009. Small molecule inhibition of a Group II chaperonin: pinpointing a loop region within the equatorial domain as necessary for protein refolding. Arch. Biochem. Biophys. 481:45–51
    [Google Scholar]
  9. 9.
    Betancourt MR, Thirumalai D. 1999. Exploring the kinetic requirements for enhancement of protein folding rates in the GroEL cavity. J. Mol. Biol. 287:627–44
    [Google Scholar]
  10. 10.
    Bigman LS, Horovitz A. 2019. Reconciling the controversy regarding the functional importance of bullet- and football-shaped GroE complexes. J. Biol. Chem. 294:13527–29
    [Google Scholar]
  11. 11.
    Brackley KI, Grantham J. 2011. Interactions between the actin filament capping and severing protein gelsolin and the molecular chaperone CCT: evidence for nonclassical substrate interactions. Cell Stress Chaperones 16:173–79
    [Google Scholar]
  12. 12.
    Camasses A, Bodganova A, Shevchenko A, Zachariae W. 2003. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol. Cell 12:87–100
    [Google Scholar]
  13. 13.
    Carranza G, Castaño R, Fanarraga ML, Villegas JC, Gonçalves J et al. 2013. Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics. Cell. Mol. Life Sci. 70:357–71
    [Google Scholar]
  14. 14.
    Chagoyen M, Carrascosa JL, Pazos F, Valpuesta JM. 2014. Molecular determinants of the ATP hydrolysis asymmetry of the CCT chaperonin complex. Proteins 82:703–7
    [Google Scholar]
  15. 15.
    Chapman E, Farr GW, Usaite R, Furtak K, Fenton WA et al. 2006. Global aggregation of newly translated proteins in an Escherichia coli strain deficient of the chaperonin GroEL. PNAS 103:15800–5
    [Google Scholar]
  16. 16.
    Chatellier J, Hill F, Lund PA, Fersht AR. 1998. In vivo activities of GroEL minichaperones. PNAS 95:9861–66
    [Google Scholar]
  17. 17.
    Chaudhuri TK, Farr GW, Fenton WA, Rospert S, Horwich AL 2001. GroEL/ES-mediated folding of a protein too large to be encapsulated. Cell 107:235–46
    [Google Scholar]
  18. 18.
    Chen X, Sullivan DS, Huffaker TC. 1994. Two yeast genes with similarities to TCP-1 are required for microtubule and actin function in vivo. PNAS 91:9111–15
    [Google Scholar]
  19. 19.
    Cuéllar J, Ludlam WG, Tensmeyer NC, Aoba T, Dhavale M et al. 2019. Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly. Nat. Commun. 10:2865
    [Google Scholar]
  20. 20.
    Cuéllar J, Martín-Benito J, Scheres SH, Sousa R, Moro F et al. 2008. The structure of CCT-Hsc70NBD suggests a mechanism for Hsp70 delivery of substrates to the chaperonin. Nat. Struct. Mol. Biol. 15:858–64
    [Google Scholar]
  21. 21.
    Danziger O, Shimon L, Horovitz A 2006. Glu257 in GroEL is a sensor involved in coupling polypeptide substrate binding to stimulation of ATP hydrolysis. Protein Sci 15:1270–76
    [Google Scholar]
  22. 22.
    Dekker C, Stirling PC, McCormack EA, Filmore H, Paul A et al. 2008. The interaction network of the chaperonin CCT. EMBO J 27:1827–39
    [Google Scholar]
  23. 23.
    Ditzel L, Löwe J, Stock D, Stetter KO, Huber H et al. 1998. Crystal structure of the thermosome, the archaeal chaperonin and homolog of CCT. Cell 93:125–38
    [Google Scholar]
  24. 24.
    Dyachenko A, Gruber R, Shimon L, Horovitz A, Sharon M. 2013. Allosteric mechanisms can be distinguished using structural mass spectrometry. PNAS 110:7235–39
    [Google Scholar]
  25. 25.
    Ellis RJ. 1994. Molecular chaperones: opening and closing the Anfinsen cage. Curr. Biol. 4:633–35
    [Google Scholar]
  26. 26.
    Fei X, Yang D, LaRonde-LeBlanc N, Lorimer GH. 2013. Crystal structure of a GroEL-ADP complex in the relaxed allosteric state at 2.7 Å resolution. PNAS 110:E2958–66
    [Google Scholar]
  27. 27.
    Feldman DE, Thulasariman V, Ferreyra RG, Frydman J. 1999. Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TriC. Mol. Cell 4:1051–61
    [Google Scholar]
  28. 28.
    Ferreiro DU, Komives EA, Wolynes PG. 2014. Frustration in biomolecules. Q. Rev. Biophys. 47:285–363
    [Google Scholar]
  29. 29.
    Finka A, Goloubinoff P. 2013. Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis. Cell Stress Chaperones 18:591–605
    [Google Scholar]
  30. 30.
    Franck JM, Sokolovski M, Kessler N, Matalon E, Gordon-Grossman M et al. 2014. Probing water density and dynamics in the chaperonin GroEL cavity. J. Am. Chem. Soc. 136:9396–403
    [Google Scholar]
  31. 31.
    Fujiwara K, Ishihama Y, Nakahigashi K, Soga T, Taguchi H. 2010. A systematic survey of in vivo obligate chaperonin-dependent substrates. EMBO J 29:1552–64
    [Google Scholar]
  32. 32.
    Gestaut D, Limatola A, Joachimiak L, Frydman J 2019. The ATP-powered gymnastics of TRiC/CCT: an asymmetric protein folding machine with a symmetric origin story. Curr. Opin. Struct. Biol. 55:50–58
    [Google Scholar]
  33. 33.
    Gestaut D, Roh SH, Ma B, Pintilie G, Joachimiak LA et al. 2019. The chaperonin TRiC/CCT associates with prefoldin through a conserved electrostatic interface essential for cellular proteostasis. Cell 177:751–65
    [Google Scholar]
  34. 34.
    Gomez-Llorente Y, Jebara F, Patra M, Malik R, Nisemblat S et al. 2020. Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin. Nat. Commun. 11:1916
    [Google Scholar]
  35. 35.
    Gómez-Puertas P, Martín-Benito J, Carrascosa JL, Willison KR, Valpuesta JM. 2004. The substrate recognition mechanisms in chaperonins. J. Mol. Recognit. 17:85–94
    [Google Scholar]
  36. 36.
    Gong Y, Kakihara Y, Krogan N, Greenblatt J, Emili A et al. 2009. An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell. Mol. Syst. Biol. 5:275
    [Google Scholar]
  37. 37.
    Gruber R, Horovitz A. 2016. Allosteric mechanisms in chaperonin machines. Chem. Rev. 116:6588–606
    [Google Scholar]
  38. 38.
    Gruber R, Levitt M, Horovitz A. 2017. Sequential allosteric mechanism of ATP hydrolysis by the CCT/TRiC chaperone is revealed through Arrhenius analysis. PNAS 114:5189–94
    [Google Scholar]
  39. 39.
    Gupta AJ, Haldar S, Miličić G, Hartl FU, Hayer-Hartl M. 2014. Active cage mechanism of chaperonin-assisted protein folding demonstrated at single-molecule level. J. Mol. Biol. 426:2739–54
    [Google Scholar]
  40. 40.
    Hayer-Hartl M, Bracher A, Hartl FU. 2016. The GroEL-GroES chaperonin machine: a nano-cage for protein folding. Trends Biochem. Sci. 41:62–76
    [Google Scholar]
  41. 41.
    Henderson B, Fares MA, Lund PA. 2013. Chaperonin 60: a paradoxical, evolutionary conserved protein family with multiple moonlighting functions. Biol. Rev. Camb. Philos. Soc. 88:955–87
    [Google Scholar]
  42. 42.
    Herzog F, Kahraman A, Boehringer D, Mak R, Bracher A et al. 2012. Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry. Science 337:1348–52
    [Google Scholar]
  43. 43.
    Hofmann H, Hillger F, Pfeil SH, Hoffmann A, Streich D et al. 2010. Single-molecule spectroscopy of protein folding in a chaperonin cage. PNAS 107:11793–98
    [Google Scholar]
  44. 44.
    Hong S, Choi G, Park S, Chung AS, Hunter E, Rhee SS 2001. Type D retrovirus Gag polyprotein interacts with the cytosolic TriC. J. Virol. 75:2526–34
    [Google Scholar]
  45. 45.
    Horst R, Fenton WA, Englander SW, Wüthrich K, Horwich AL 2007. Folding trajectories of human dihydrofolate reductase inside the GroEL-GroES chaperonin cavity and free in solution. PNAS 104:20788–92
    [Google Scholar]
  46. 46.
    Horwich AL, Fenton WA. 2020. Chaperonin-assisted protein folding: a chronologue. Q. Rev. Biophys. 53:e4
    [Google Scholar]
  47. 47.
    Hunt JF, Weaver AJ, Landry SJ, Gierasch L, Deisenhofer J 1996. The crystal structure of the GroES co-chaperonin at 2.8 Å resolution. Nature 379:37–45
    [Google Scholar]
  48. 48.
    Hyeon C, Lorimer GH, Thirumalai D. 2006. Dynamics of allosteric transitions in GroEL. PNAS 103:18939–44
    [Google Scholar]
  49. 49.
    Inbar E, Horovitz A. 1997. GroES promotes the T to R transition of the GroEL ring distal to GroES in the GroEL-GroES complex. Biochemistry 36:12276–81
    [Google Scholar]
  50. 50.
    Itzhaki LS, Otzen DE, Fersht AR. 1995. Nature and consequences of GroEL-protein interactions. Biochemistry 34:14581–87
    [Google Scholar]
  51. 51.
    Ivankov DN, Finkelstein AV. 2004. Prediction of protein folding rates from the amino acid sequence-predicted secondary structure. PNAS 101:8942–44
    [Google Scholar]
  52. 52.
    Jensen PR, Loman L, Petra B, van der Weijden C, Westerhoff HV 1995. Energy buffering of DNA structure fails when Escherichia coli runs out of substrate. J. Bacteriol. 177:3420–26
    [Google Scholar]
  53. 53.
    Jin M, Han W, Liu C, Zang Y, Li J et al. 2019. An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity. PNAS 116:19513–22
    [Google Scholar]
  54. 54.
    Kabir MA, Kaminska J, Segel GB, Bethlendy G, Lin P et al. 2005. Physiological effects of unassembled chaperonin Cct in the yeast Saccharomyces cerevisiae. Yeast 22:219–39
    [Google Scholar]
  55. 55.
    Kalisman N, Adams CM, Levitt M 2012. Subunit order of eukaryotic TRiC/CCT chaperonin by cross-linking, mass spectrometry, and combinatorial homology modeling. PNAS 109:2884–89
    [Google Scholar]
  56. 56.
    Kashuba E, Pokrovskaja K, Klein G, Szekely L. 1999. Epstein-Barr virus-encoded nuclear protein EBNA-3 interacts with the ε-subunit of the T-complex protein 1 chaperonin complex. J. Hum. Virol. 2:33–37
    [Google Scholar]
  57. 57.
    Kerner MJ, Naylor DJ, Ishihama Y, Maier T, Chang HC et al. 2005. Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli. Cell 122:209–20
    [Google Scholar]
  58. 58.
    Kipnis Y, Papo N, Haran G, Horovitz A. 2007. Concerted ATP-induced allosteric transitions in GroEL facilitate release of protein substrate domains in an all-or-none manner. PNAS 104:3119–24
    [Google Scholar]
  59. 59.
    Klumpp M, Baumeister W, Essen LO. 1997. Structure of the substrate binding domain of the thermosome, an archaeal group II chaperonin. Cell 91:263–70
    [Google Scholar]
  60. 60.
    Knowlton JJ, Gestaut D, Ma B, Taylor G, Seven AB et al. 2021. Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network. PNAS 118:e2018127118
    [Google Scholar]
  61. 61.
    Koculi E, Thirumalai D. 2021. Retardation of folding rates of substrate proteins in the nanocage of GroEL. Biochemistry 60:460–64
    [Google Scholar]
  62. 62.
    Korobko I, Mazal H, Haran G, Horovitz A 2020. Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization. eLife 9:e56511
    [Google Scholar]
  63. 63.
    Koshland DE Jr., Némethy G, Filmer D 1966. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5:365–85
    [Google Scholar]
  64. 64.
    Leitner A, Joachimiak LA, Bracher A, Mönkemeyer L, Walzthoeni T et al. 2012. The molecular architecture of the eukaryotic chaperonin TRiC/CCT. Structure 20:814–25
    [Google Scholar]
  65. 65.
    Libich DS, Tugarinov V, Clore GM. 2015. Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly demonstrated using multinuclear relaxation-based NMR. PNAS 112:8817–23
    [Google Scholar]
  66. 66.
    Lingappa JR, Martin RL, Wong ML, Ganem D, Welch WJ, Lingappa VR 1994. A eukaryotic cytosolic chaperonin is associated with a high molecular weight intermediate in the assembly of hepatitis B virus capsid, a multimeric particle. J. Cell Biol. 125:99–111
    [Google Scholar]
  67. 67.
    Llorca O, Martín-Benito J, Grantham J, Ritco-Vonsovici M, Willison KR et al. 2001. The “sequential allosteric ring” mechanism in the eukaryotic chaperonin-assisted folding of actin and tubulin. EMBO J 20:4065–75
    [Google Scholar]
  68. 68.
    Llorca O, McCormack EA, Hynes G, Grantham J, Cordell J et al. 1999. Eukaryotic type II chaperonin CCT interacts with actin through specific subunits. Nature 402:693–96
    [Google Scholar]
  69. 69.
    Lorimer GH. 1996. A quantitative assessment of the role of the chaperonin proteins in protein folding in vivo. FASEB J 10:5–9
    [Google Scholar]
  70. 70.
    Lukov GL, Hu T, McLaughlin JN, Hamm HE, Willardson BM. 2005. Phosducin-like protein acts as a molecular chaperone for G protein βγ dimer assembly. EMBO J 24:1965–75
    [Google Scholar]
  71. 71.
    Ma J, Karplus M 1998. The allosteric mechanism of the chaperonin GroEL: a dynamic analysis. PNAS 95:8502–7
    [Google Scholar]
  72. 72.
    Macro N, Chen L, Yang Y, Mondal T, Wang L et al. 2021. Slowdown of water dynamics from the top to the bottom of the GroEL cavity. J. Phys. Chem. Lett. 12:5723–30
    [Google Scholar]
  73. 73.
    Martín-Benito J, Bertrand S, Hu T, Ludtke PJ, McLaughlin JN et al. 2004. Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein. PNAS 101:17410–15
    [Google Scholar]
  74. 74.
    Martín-Benito J, Boskovic J, Gómez-Puertas P, Carrascosa JL, Simons CT et al. 2002. Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT. EMBO J 21:6377–86
    [Google Scholar]
  75. 75.
    Martín-Cofreces NB, Chichón FJ, Calvo E, Torralba D, Bustos-Morán E et al. 2020. The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles. Sci. Adv. 6:eabb7242
    [Google Scholar]
  76. 76.
    McLaughlin JN, Thulin CD, Hart SJ, Resing KA, Ahn NG, Willardson BM 2002. Regulatory interaction of phosducin-like protein with the cytosolic chaperonin complex. PNAS 99:7962–67
    [Google Scholar]
  77. 77.
    Melki R, Batelier G, Soulié S, Williams RC Jr. 1997. Cytoplasmic chaperonin containing TCP-1: structural and functional characterization. Biochemistry 36:5817–26
    [Google Scholar]
  78. 78.
    Melki R, Vainberg IE, Chow RL, Cowan NJ. 1993. Chaperonin-mediated folding of vertebrate actin-related protein and gamma-tubulin. J. Cell Biol. 122:1301–10
    [Google Scholar]
  79. 79.
    Monod J, Wyman J, Changuex JP. 1965. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12:88–118
    [Google Scholar]
  80. 80.
    Motojima F, Yoshida M. 2010. Polypeptide in the chaperonin cage partly protrudes out and then folds inside or escapes outside. EMBO J 29:4008–19
    [Google Scholar]
  81. 81.
    Muñoz IG, Yébenes H, Zhou M, Mesa P, Serna M et al. 2010. Crystal structure of the open conformation of the mammalian chaperonin CCT in complex with tubulin. Nat. Struct. Mol. Biol. 18:14–19
    [Google Scholar]
  82. 82.
    Nagpal S, Tiwari S, Mapa K, Thukral L 2015. Decoding structural properties of a partially unfolded protein substrate: en route to chaperone binding. PLOS Comput. Biol. 11:e1004496
    [Google Scholar]
  83. 83.
    Nielsen KL, Cowan NJ. 1998. A single ring is sufficient for productive chaperonin-mediated folding in vivo. Mol. Cell 2:93–99
    [Google Scholar]
  84. 84.
    Niwa T, Fujiwara K, Taguchi H. 2016. Identification of novel in vivo obligate GroEL/ES substrates based on data from a cell-free proteomics approach. FEBS Lett 590:251–57
    [Google Scholar]
  85. 85.
    Niwa T, Ying BW, Saito K, Jin W, Takada S et al. 2009. Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins. PNAS 106:4201–6
    [Google Scholar]
  86. 86.
    Noivirt-Brik O, Unger R, Horovitz A. 2007. Low folding propensity and high translation efficiency distinguish in vivo substrates of GroEL from other Escherichia coli proteins. Bioinformatics 23:3276–79
    [Google Scholar]
  87. 87.
    Noshiro D, Ando T. 2018. Substrate protein dependence of GroEL-GroES interaction cycle revealed by high-speed atomic force microscopy imaging. Philos. Trans. R. Soc. Lond. B 373:20170180
    [Google Scholar]
  88. 88.
    Papo N, Kipnis Y, Haran G, Horovitz A. 2008. Concerted release of substrate domains from GroEL by ATP is demonstrated with FRET. J. Mol. Biol. 380:717–25
    [Google Scholar]
  89. 89.
    Pappenberger G, Wilsher JA, Roe SM, Counsell DJ, Willison KR, Pearl LH. 2002. Crystal structure of the CCTγ apical domain: implications for substrate binding to the eukaryotic cytosolic chaperonin. J. Mol. Biol. 318:1367–79
    [Google Scholar]
  90. 90.
    Passmore LA, McCormack EA, Au SWN, Paul A, Willison KR et al. 2003. Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. EMBO J 22:786–96
    [Google Scholar]
  91. 91.
    Pereira JH, Ralston CY, Douglas NR, Meyer D, Knee KM et al. 2010. Crystal structures of a group II chaperonin reveal the open and closed states associated with the protein folding cycle. J. Biol. Chem. 285:27958–66
    [Google Scholar]
  92. 92.
    Plaxco KW, Simons KT, Baker D. 1998. Contact order, transition state placement and the refolding rates of single domain proteins. J. Mol. Biol. 277:985–94
    [Google Scholar]
  93. 93.
    Plimpton RL, Cuéllar J, Lai CW, Aoba T, Makaju A et al. 2015. Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly. PNAS 112:2413–18
    [Google Scholar]
  94. 94.
    Priya S, Sharma SK, Sood V, Mattoo RU, Finka A et al. 2013. GroEL and CCT are catalytic unfoldases mediating out-of-cage polypeptide refolding without ATP. PNAS 110:7199–204
    [Google Scholar]
  95. 95.
    Ramakrishnan R, Houben B, Rousseau F, Schymkowitz J. 2019. Differential proteostatic regulation of insoluble and abundant proteins. Bioinformatics 35:4098–107
    [Google Scholar]
  96. 96.
    Ranson NA, Dunster NJ, Burston SG, Clarke AR. 1995. Chaperonins can catalyse the reversal of early aggregation steps when a protein misfolds. J. Mol. Biol. 250:581–86
    [Google Scholar]
  97. 97.
    Reissmann S, Joachimiak LA, Chen B, Meyer AS, Nguyen A, Frydman J. 2012. A gradient of ATP affinities generates an asymmetric power stroke driving the chaperonin TRIC/CCT folding cycle. Cell Rep 2:866–77
    [Google Scholar]
  98. 98.
    Rivenzon-Segal D, Wolf SG, Shimon L, Willison KR, Horovitz A 2005. Sequential ATP-induced allosteric transitions of the cytoplasmic chaperonin-containing TCP-1 revealed by EM analysis. Nat. Struct. Mol. Biol. 12:233–37
    [Google Scholar]
  99. 99.
    Rizzolo K, Huen J, Kumar A, Phanse S, Vlasblom J et al. 2017.. Features of the chaperone cellular network revealed through systematic interaction mapping. Cell Rep 20:2735–48
    [Google Scholar]
  100. 100.
    Rye HS, Burston SG, Fenton WA, Beechem JM, Xu Z et al. 1997. Distinct actions of cis and trans ATP within the double ring of the chaperonin GroEL. Nature 388:792–98
    [Google Scholar]
  101. 101.
    Saibil HR, Fenton WA, Clare DK, Horwich AL 2013. Structure and allostery of the chaperonin GroEL. J. Mol. Biol. 425:1476–87
    [Google Scholar]
  102. 102.
    Sergeeva OA, Haase-Pettingell C, King JA. 2019. Co-expression of CCT subunits hints at TRiC assembly. Cell Stress Chaperones 24:1055–65
    [Google Scholar]
  103. 103.
    Skjærven L, Cuellar J, Martinez A, Valpuesta JM. 2015. Dynamics, flexibility, and allostery in molecular chaperonins. FEBS Lett 589:2522–32
    [Google Scholar]
  104. 104.
    Smith TF, Gaitatzes C, Saxena K, Neer EJ. 1999. The WD40 repeat: a common architecture for diverse functions. Trends Biochem. Sci. 24:181–85
    [Google Scholar]
  105. 105.
    Spiess C, Miller EJ, McClellan AJ, Frydman J. 2006. Identification of the TRiC/CCT substrate binding sites uncovers the function of subunit diversity in eukaryotic chaperonins. Mol. Cell 24:25–37
    [Google Scholar]
  106. 106.
    Srikakulam R, Winkelmann DA. 1999. Myosin II folding is mediated by a molecular chaperonin. J. Biol. Chem. 274:27265–73
    [Google Scholar]
  107. 107.
    Stan G, Brooks BR, Lorimer GH, Thirumalai D 2005. Identifying natural substrates for chaperonins using a sequence-based approach. Protein Sci 14:193–201
    [Google Scholar]
  108. 108.
    Stirling PC, Cuéllar J, Alfaro GA, El Khadali F, Beh CT et al. 2006. PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with substrates. J. Biol. Chem. 281:7012–21
    [Google Scholar]
  109. 109.
    Stuart SF, Leatherbarrow RJ, Willison KR. 2011. A two-step mechanism for the folding of actin by the yeast cytosolic chaperonin. J. Biol. Chem. 286:178–84
    [Google Scholar]
  110. 110.
    Suzuki M, Ueno T, Iizuka R, Miura T, Zako T et al. 2008. Effect of the C-terminal truncation on the functional cycle of chaperonin GroEL: implication that the C-terminal region facilitates the transition from the folding-arrested to the folding-competent state. J. Biol. Chem. 283:23931–39
    [Google Scholar]
  111. 111.
    Svanström A, Grantham J. 2016. The molecular chaperone CCT modulates the activity of the actin filament severing and capping protein gelsolin in vitro. Cell Stress Chaperones 21:55–62
    [Google Scholar]
  112. 112.
    Taguchi H. 2015. Reaction cycle of chaperonin GroEL via symmetric “football” intermediate. J. Mol. Biol. 427:2912–18
    [Google Scholar]
  113. 113.
    Taguchi H, Tsukuda K, Motojima F, Koike-Takeshita A, Yoshida M. 2004. BeFx stops the chaperonin cycle of GroEL-GroES and generates a complex with double folding chambers. J. Biol. Chem. 279:45737–43
    [Google Scholar]
  114. 114.
    Tang YC, Chang HC, Roeben A, Wischnewski D, Wischnewski N et al. 2006. Structural features of the GroEL-GroES nano-cage required for rapid folding of encapsulated protein. Cell 125:903–14
    [Google Scholar]
  115. 115.
    Tartaglia GG, Dobson CM, Hartl FU, Vendruscolo M. 2010. Physicochemical determinants of chaperone requirements. J. Mol. Biol. 400:579–88
    [Google Scholar]
  116. 116.
    Thirumalai D, Lorimer GH. 2001. Chaperonin-mediated protein folding. Annu. Rev. Biophys. Biomol. Struct. 30:245–69
    [Google Scholar]
  117. 117.
    Thirumalai D, Lorimer GH, Hyeon C. 2020. Iterative annealing mechanism explains the functions of the GroEL and RNA chaperones. Protein Sci 29:360–77
    [Google Scholar]
  118. 118.
    Todd MJ, Lorimer GH, Thirumalai D. 1996. Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism. PNAS 93:4030–35
    [Google Scholar]
  119. 119.
    Tracy CM, Gray AJ, Cuéllar J, Shaw TS, Howlett AC et al. 2014. Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate β-tubulin folding. J. Biol. Chem. 289:4490–502
    [Google Scholar]
  120. 120.
    Tyagi NK, Fenton WA, Deniz AA, Horwich AL. 2011. Double mutant MBP refolds at same rate in free solution as inside the GroEL/GroES chaperonin chamber when aggregation in free solution is prevented. FEBS Lett 585:1969–72
    [Google Scholar]
  121. 121.
    Vallin J, Córdoba-Beldad CM, Grantham J. 2021. Sequestration of the transcription factor STAT3 by the molecular chaperone CCT: a potential mechanism for modulation of STAT3 phosphorylation. J. Mol. Biol. 433:166958
    [Google Scholar]
  122. 122.
    Valpuesta JM, Martín-Benito J, Gómez-Puertas P, Carrascosa JL, Willison KR. 2002. Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett 529:11–16
    [Google Scholar]
  123. 123.
    Viitanen PV, Gatenby AA, Lorimer GH. 1992. Purified chaperonin 60 (groEL) interacts with the nonnative states of a multitude of Escherichia coli proteins. Protein Sci 1:363–69
    [Google Scholar]
  124. 124.
    Villebeck L, Moparthi SB, Lindgren M, Hammarström P, Jonsson BH. 2007. Domain-specific chaperone-induced expansion is required for β-actin folding: a comparison of β-actin conformations upon interactions with GroEL and tail-less complex polypeptide 1 ring complex (TRiC). Biochemistry 46:12639–47
    [Google Scholar]
  125. 125.
    Villebeck L, Persson M, Luan SL, Hammarström P, Lindgren M, Jonsson BH. 2007. Conformational rearrangements of tail-less complex polypeptide 1 (TCP-1) ring complex (TRiC)-bound actin. Biochemistry 46:5083–93
    [Google Scholar]
  126. 126.
    Vinh DB, Drubin DG. 1994. A yeast TCP-1-like protein is required for actin function in vivo. PNAS 91:9116–20
    [Google Scholar]
  127. 127.
    Weaver J, Jiang M, Roth A, Puchalla J, Zhang J, Rye HS. 2017. GroEL actively stimulates folding of the endogenous substrate protein PepQ. Nat. Commun. 8:15934
    [Google Scholar]
  128. 128.
    Weaver J, Rye HS. 2014. The C-terminal tails of the bacterial chaperonin GroEL stimulate protein folding by directly altering the conformation of a substrate protein. J. Biol. Chem. 289:23219–32
    [Google Scholar]
  129. 129.
    Weissman JS, Rye HS, Fenton WA, Beechem JM, Horwich AL. 1996. Characterization of the active intermediate of a GroEL-GroES-mediated protein folding reaction. Cell 84:481–90
    [Google Scholar]
  130. 130.
    Willison KR. 2018. The structure and evolution of eukaryotic chaperonin-containing TCP-1 and its mechanism that folds actin into a protein spring. Biochem. J. 475:3009–34
    [Google Scholar]
  131. 131.
    Willison KR. 2018. The substrate specificity of eukaryotic cytosolic chaperonin CCT. Philos. Trans. R. Soc. B 373:20170192
    [Google Scholar]
  132. 132.
    Xu Z, Horwich AL, Sigler PB. 1997. The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex. Nature 388:741–50
    [Google Scholar]
  133. 133.
    Yaginuma H, Kawai S, Tabata KV, Tomiyama K, Kakizuka A et al. 2014. Diversity in ATP concentrations in a single bacterial cell population revealed by quantitative single-cell imaging. Sci. Rep. 4:6522
    [Google Scholar]
  134. 134.
    Yam AY, Xia Y, Lin HT, Burlingame A, Gerstein M, Frydman J. 2008. Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. Nat. Struct. Mol. Biol. 15:1255–62
    [Google Scholar]
  135. 135.
    Yan X, Shi Q, Bracher A, Miličić G, Singh AK et al. 2018. GroEL ring separation and exchange in the chaperonin reaction. Cell 172:605–17
    [Google Scholar]
  136. 136.
    Yang D, Ye X, Lorimer GH 2013. Symmetric GroEL:GroES2 complexes are the protein-folding functional form of the chaperonin nanomachine. PNAS 110:E4298–305
    [Google Scholar]
  137. 137.
    Ye X, Lorimer GH 2013. Substrate protein switches GroE chaperonins from asymmetric to symmetric cycling by catalyzing nucleotide exchange. PNAS 110:E4289–97
    [Google Scholar]
  138. 138.
    Ye X, Mayne L, Kan ZY, Englander SW. 2018. Folding of maltose binding protein outside of and in GroEL. PNAS 115:519–24
    [Google Scholar]
  139. 139.
    Yebenes H, Mesa P, Munoz IG, Montoya G, Valpuesta JM. 2011. Chaperonins: two rings for folding. Trends Biochem. Sci. 36:424–32
    [Google Scholar]
  140. 140.
    Yifrach O, Horovitz A. 1994. Two lines of allosteric communication in the oligomeric chaperonin GroEL are revealed by the single mutation Arg196→Ala. J. Mol. Biol. 243:397–401
    [Google Scholar]
  141. 141.
    Yifrach O, Horovitz A. 1995. Nested cooperativity in the ATPase activity of the oligomeric chaperonin GroEL. Biochemistry 34:5303–8
    [Google Scholar]
  142. 142.
    Zahn R, Perrett S, Stenberg G, Fersht AR. 1996. Catalysis of amide proton exchange by the molecular chaperones GroEL and SecB. Science 271:642–45
    [Google Scholar]
  143. 143.
    Zhang Y, Krieger J, Mikulska-Ruminska K, Kaynak B, Sorzano COS et al. 2021. State-dependent sequential allostery exhibited by chaperonin TRiC/CCT revealed by network analysis of cryo-EM maps. Prog. Biophys. Mol. Biol. 160:104–20
    [Google Scholar]
/content/journals/10.1146/annurev-biophys-082521-113418
Loading
/content/journals/10.1146/annurev-biophys-082521-113418
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error