Repetitive Protein Unfolding by the Trans Ring of the GroEL-GroES Chaperonin Complex Stimulates Folding

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2013 Sep 12

PMID 24022487

Citations 12

Authors

Zong Lin

Jason Puchalla

Daniel Shoup

Hays S Rye

Affiliations

Soon will be listed here.

Abstract

A key constraint on the growth of most organisms is the slow and inefficient folding of many essential proteins. To deal with this problem, several diverse families of protein folding machines, known collectively as molecular chaperones, developed early in evolutionary history. The functional role and operational steps of these remarkably complex nanomachines remain subjects of active debate. Here we present evidence that, for the GroEL-GroES chaperonin system, the non-native substrate protein enters the folding cycle on the trans ring of the double-ring GroEL-ATP-GroES complex rather than the ADP-bound complex. The properties of this ATP complex are designed to ensure that non-native substrate protein binds first, followed by ATP and finally GroES. This binding order ensures efficient occupancy of the open GroEL ring and allows for disruption of misfolded structures through two phases of multiaxis unfolding. In this model, repeated cycles of partial unfolding, followed by confinement within the GroEL-GroES chamber, provide the most effective overall mechanism for facilitating the folding of the most stringently dependent GroEL substrate proteins.

Citing Articles

How soluble misfolded proteins bypass chaperones at the molecular level.

Halder R, Nissley D, Sitarik I, Jiang Y, Rao Y, Vu Q Nat Commun. 2023; 14(1):3689.

PMID: 37344452 PMC: 10284856. DOI: 10.1038/s41467-023-38962-z.

The Impact of Hidden Structure on Aggregate Disassembly by Molecular Chaperones.

Shoup D, Roth A, Puchalla J, Rye H Front Mol Biosci. 2022; 9():915307.

PMID: 35874607 PMC: 9302491. DOI: 10.3389/fmolb.2022.915307.

Temperature Regulates Stability, Ligand Binding (Mg and ATP), and Stoichiometry of GroEL-GroES Complexes.

Walker T, Shirzadeh M, Sun H, McCabe J, Roth A, Moghadamchargari Z J Am Chem Soc. 2022; 144(6):2667-2678.

PMID: 35107280 PMC: 8939001. DOI: 10.1021/jacs.1c11341.

Monitoring site-specific conformational changes in real-time reveals a misfolding mechanism of the prion protein.

Sengupta I, Udgaonkar J Elife. 2019; 8.

PMID: 31232689 PMC: 6590988. DOI: 10.7554/eLife.44698.

Temperature-Dependent Nanomechanics and Topography of Bacteriophage T7.

Voros Z, Csik G, Herenyi L, Kellermayer M J Virol. 2018; 92(20).

PMID: 30089696 PMC: 6158431. DOI: 10.1128/JVI.01236-18.

References

Martin J, Langer T, Boteva R, Schramel A, Horwich A, Hartl F . Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate. Nature. 1991; 352(6330):36-42. DOI: 10.1038/352036a0. View

Todd M, Lorimer G, Thirumalai D . Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism. Proc Natl Acad Sci U S A. 1996; 93(9):4030-5. PMC: 39481. DOI: 10.1073/pnas.93.9.4030. View

Madan D, Lin Z, Rye H . Triggering protein folding within the GroEL-GroES complex. J Biol Chem. 2008; 283(46):32003-13. PMC: 2581556. DOI: 10.1074/jbc.M802898200. View

Badcoe I, Smith C, Wood S, Halsall D, HOLBROOK J, Lund P . Binding of a chaperonin to the folding intermediates of lactate dehydrogenase. Biochemistry. 1991; 30(38):9195-200. DOI: 10.1021/bi00102a010. View

Saibil H, Zheng D, Roseman A, Hunter A, Watson G, Chen S . ATP induces large quaternary rearrangements in a cage-like chaperonin structure. Curr Biol. 1993; 3(5):265-73. DOI: 10.1016/0960-9822(93)90176-o. View

Hofmann H, Hillger F, Pfeil S, Hoffmann A, Streich D, Haenni D . Single-molecule spectroscopy of protein folding in a chaperonin cage. Proc Natl Acad Sci U S A. 2010; 107(26):11793-8. PMC: 2900638. DOI: 10.1073/pnas.1002356107. View

Weissman J, Rye H, Fenton W, Beechem J, Horwich A . Characterization of the active intermediate of a GroEL-GroES-mediated protein folding reaction. Cell. 1996; 84(3):481-90. DOI: 10.1016/s0092-8674(00)81293-3. View

Horwich A, Fenton W . Chaperonin-mediated protein folding: using a central cavity to kinetically assist polypeptide chain folding. Q Rev Biophys. 2009; 42(2):83-116. DOI: 10.1017/S0033583509004764. View

Kerner M, Naylor D, Ishihama Y, Maier T, Chang H, Stines A . Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli. Cell. 2005; 122(2):209-20. DOI: 10.1016/j.cell.2005.05.028. View

10.

Lin Z, Madan D, Rye H . GroEL stimulates protein folding through forced unfolding. Nat Struct Mol Biol. 2008; 15(3):303-11. PMC: 3744391. DOI: 10.1038/nsmb.1394. View

11.

Grason J, Gresham J, Widjaja L, Wehri S, Lorimer G . Setting the chaperonin timer: the effects of K+ and substrate protein on ATP hydrolysis. Proc Natl Acad Sci U S A. 2008; 105(45):17334-8. PMC: 2580752. DOI: 10.1073/pnas.0807429105. View

12.

Rye H, Burston S, Fenton W, Beechem J, Xu Z, SIGLER P . Distinct actions of cis and trans ATP within the double ring of the chaperonin GroEL. Nature. 1997; 388(6644):792-8. DOI: 10.1038/42047. View

13.

Schmidt M, Buchner J, Todd M, Lorimer G, Viitanen P . On the role of groES in the chaperonin-assisted folding reaction. Three case studies. J Biol Chem. 1994; 269(14):10304-11. View

14.

Hartl F, Bracher A, Hayer-Hartl M . Molecular chaperones in protein folding and proteostasis. Nature. 2011; 475(7356):324-32. DOI: 10.1038/nature10317. View

15.

Sameshima T, Iizuka R, Ueno T, Wada J, Aoki M, Shimamoto N . Single-molecule study on the decay process of the football-shaped GroEL-GroES complex using zero-mode waveguides. J Biol Chem. 2010; 285(30):23159-64. PMC: 2906309. DOI: 10.1074/jbc.M110.122101. View

16.

Sameshima T, Ueno T, Iizuka R, Ishii N, Terada N, Okabe K . Football- and bullet-shaped GroEL-GroES complexes coexist during the reaction cycle. J Biol Chem. 2008; 283(35):23765-73. PMC: 3259762. DOI: 10.1074/jbc.M802541200. View

17.

Yifrach O, Horovitz A . Two lines of allosteric communication in the oligomeric chaperonin GroEL are revealed by the single mutation Arg196-->Ala. J Mol Biol. 1994; 243(3):397-401. DOI: 10.1006/jmbi.1994.1667. View

18.

Kim S, Miller E, Frydman J, Moerner W . Action of the chaperonin GroEL/ES on a non-native substrate observed with single-molecule FRET. J Mol Biol. 2010; 401(4):553-63. PMC: 2927214. DOI: 10.1016/j.jmb.2010.06.050. View

19.

Lin Z, Rye H . GroEL-mediated protein folding: making the impossible, possible. Crit Rev Biochem Mol Biol. 2006; 41(4):211-39. PMC: 3783267. DOI: 10.1080/10409230600760382. View

20.

Braig K, Otwinowski Z, Hegde R, Boisvert D, Joachimiak A, Horwich A . The crystal structure of the bacterial chaperonin GroEL at 2.8 A. Nature. 1994; 371(6498):578-86. DOI: 10.1038/371578a0. View