The reaction cycle of GroEL and GroES in chaperonin-assisted protein folding

Martin, Jörg; Mayhew, Mark; Langer, Thomas; Hartl, Ulrich

doi:10.1038/366228a0

Cited by 283 publications

(223 citation statements)

References 31 publications

Supporting

Mentioning

212

Contrasting

Order By: Relevance

“…Due to the fact that differences in this range have been described already as possible classes reflecting an intrinsic structural heteronegeity of GroEL-GroES complexes [19], the real significance of these differences between ATP, ADP and non-hydrolizable ATP demand further analysis of more numerous particle populations to yield higher resolution and to allow better classification procedures. Most of the current models for the chaperonin-assisted folding mechanism are based on reaction cycles that involve the sequential interaction of GroEL and GroES correlating with cycles of ATP binding and hydrolysis [17,20]. All these models rely on the functionality of asymmetric GroEL-GroES complexes where one GroES complex binds to one end of the GroEL cylinder, although both ends are potentially capable of binding GroES [ 17,3 1,321.…”

Section: Structure Of the Groeggroes Complex Formed Inmentioning

confidence: 99%

See 1 more Smart Citation

The formation of symmetrical GroEL‐GroES complexes in the presence of ATP

et al. 1994

View full text Add to dashboard Cite

The incubation of chaperonins cpn60 (GroEL) and cpnl0 (GroES) from E. coli in the presence of Mg-ATP and KC1 generates the formation, as revealed by electron microscopy, of GroEL-GroES complexes with a symmetrical shape in which one toroidal GroES oligomer is bound to each end of the tetradecameric GroEL aggregate (1: 2 GroEL : GroES oligomer molar ratio). The symmetrical complexes are not observed in the presence of ADP or the non-hydrolyzable ATP analog, ATPyS, where only asymmetrical complexes (1: 1 GroEL: GroES oligomer molar ratio) are formed.These results suggest that ATP hydrolysis is required for the formation of symmetrical complexes.

show abstract

Section: Structure Of the Groeggroes Complex Formed Inmentioning

confidence: 99%

“…Upon exchange of ADP for ATP, GroES binds again to GroEL and the hydrolysis of ATP releases the bound protein for folding. Par-tially folded protein can repeat this charge-discharge cycle until folding is complete [17].…”

Section: Introductionmentioning

confidence: 99%

The formation of symmetrical GroEL‐GroES complexes in the presence of ATP

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Complete chaperonin-assisted folding of DHFR to its native state requires several cycles of ATP hydrolysis, which is accompanied by iterative rounds of binding and release of the substrate protein tolfrom the surface of the GroEL central cavity (Martin et al, 1993). Although ATP hydrolysis is required for GroELassisted folding of many proteins, there is little detailed knowledge about the role that substrate cycling plays in the mechanism of GroEL-assisted folding.…”

Section: Msmentioning

confidence: 99%

“…Their interaction with newly synthesized proteins has been described as a sequential pathway of assisted folding (Langer et al, 1992), in which the chaperonins complete folding by guiding molecules to their ultimate native structures (Jaenicke, 1993;Ellis, 1994;Hartl et al, 1994;Hartl, 1996). One representative of this class of chaperones, the tetradecameric bacterial chaperonin GroEL, has been studied in great detail, and models for its reaction cycle with different combinations of protein substrate, nucleotides, and GroES have been proposed (Jackson et al, 1993;Martin et al, 1993;Todd et al, 1994;Burston et al, 1995;Mayhew et al, 1996;Weissman et al, 1996). Although it is now generally accepted that partially folded molecules bind and fold within the GroEL central cavity (Braig et al, 1993;Chen et al, 1994;Mayhew et al, 1996; Reprint requests to Sheena E. Radford at her present address: Department of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT; e-mail: s.e.radford@leeds.ac.uk.…”

mentioning

confidence: 99%

Significant hydrogen exchange protection in GroEL‐bound DHFR is maintained during iterative rounds of substrate cycling

Gross¹,

Robinson²,

Mayhew

et al. 1996

Protein Science

Self Cite

View full text Add to dashboard Cite

An unresolved key issue in the mechanism of protein folding assisted by the molecular chaperone GroEL is the nature of the substrate protein bound to the chaperonin at different stages of its reaction cycle. Here we describe the conformational properties of human dihydrofolate reductase (DHFR) bound to GroEL at different stages of its ATP-driven folding reaction, determined by hydrogen exchange labeling and electrospray ionization mass spectrometry. Considerable protection involving about 20 hydrogens is observed in DHFR bound to GroEL in the absence of ATP. Analysis of the line width of peaks in the mass spectra, together with fluorescence quenching and ANS binding studies, suggest that the bound DHFR is partially folded, but contains stable structure in a small region of the polypeptide chain. DHFR rebound to GroEL 3 min after initiating its folding by the addition of MgATP was also examined by hydrogen exchange, fluorescence quenching, and ANS binding. The results indicate that the extent of protection of the substrate protein rebound to GroEL is indistinguishable from that of the initial bound state. Despite this, small differences in the quenching coefficient and ANS binding properties are observed in the rebound state. On the basis of these results, we suggest that GroEL-assisted folding of DHFR occurs by minor structural adjustments to the partially folded substrate protein during iterative cycling, rather than by complete unfolding of this protein substrate on the chaperonin surface.

show abstract

“…The explanation of chaperonin function based on the marsupium model has been widely accepted since it can explain functional meaning of a central cavity of chaperonin [20][21][22]. However, several results that favor the reversion model were published recently [19,23].…”

Section: Introductionmentioning

confidence: 99%

Chaperonin releases the substrate protein in a form with tendency to aggregate and ability to rebind to chaperonin

Taguchi

Yoshida

1995

FEBS Letters

View full text Add to dashboard Cite

To know whether the protein released from chaperonin GroEL/ES is in a form committed to the native state or still an aggregatable non-native one, two experiments were carried out. Dilution of the [GroEL-substrate protein] binary complex prior to ATP addition significantly improved the yield of folding, suggesting that the released protein has a tendency to aggregate. When N-ethylmaleimide treated GroEL, which can form the binary complex but not release the bound protein, was added to the binary complex prior to ATP addition, productive folding was severely inhibited, indicating that the protein released from GroEL/ES can bind to N-ethylmaleimide treated chaperonin. These data favor the 'reservoir' or 'reversion' model, in which GroELIES acts as a buffer of folding intermediate or mediates reversion of a misfolded protein to a less folded primitive form, rather than the 'marsupium' model in which folding of the substrate protein proceeds in chaperonin.

show abstract

The reaction cycle of GroEL and GroES in chaperonin-assisted protein folding

Cited by 283 publications

References 31 publications

The formation of symmetrical GroEL‐GroES complexes in the presence of ATP

The formation of symmetrical GroEL‐GroES complexes in the presence of ATP

Significant hydrogen exchange protection in GroEL‐bound DHFR is maintained during iterative rounds of substrate cycling

Chaperonin releases the substrate protein in a form with tendency to aggregate and ability to rebind to chaperonin

Contact Info

Product

Resources

About