Chaperonin-Catalyzed Rescue of Kinetically Trapped States in Protein Folding

@article{Chakraborty2010ChaperoninCatalyzedRO,
  title={Chaperonin-Catalyzed Rescue of Kinetically Trapped States in Protein Folding},
  author={Kausik Chakraborty and Manal Chatila and Jyoti Sinha and Qiaoyun Shi and Bernhard C Poschner and Martin Sikor and Guoxin Jiang and Don C. Lamb and F. Ulrich Hartl and Manajit Hayer-Hartl},
  journal={Cell},
  year={2010},
  volume={142},
  pages={112-122}
}
GroEL and GroES form a chaperonin nano-cage for single protein molecules to fold in isolation. The folding properties that render a protein chaperonin dependent are not yet understood. Here, we address this question using a double mutant of the maltose-binding protein DM-MBP as a substrate. Upon spontaneous refolding, DM-MBP populates a kinetically trapped intermediate that is collapsed but structurally disordered. Introducing two long-range disulfide bonds into DM-MBP reduces the entropic… Expand
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Evidence is shown that the in-cage-folding and the escape occur diverging from the same intermediate complex in which polypeptide is tethered loosely to the cage and partly protrudes out of the cage. Expand
Chaperonin facilitates protein folding by avoiding initial polypeptide collapse
TLDR
Evidence is shown that the in-cage-folding and the escape occur diverging from the same intermediate complex in which polypeptide is tethered loosely to the cage and partly protrudes out of the cage. Expand
Mechanisms of folding, assembly and remodelling chaperones
end. The GroEL/ES-mediated folding of the model strate protein DM-MBP is monitored by single-molee FRET. Folding intermediate bound to GroEL shows a FRET efficiency distribution. Upon refolding,Expand
Folding of maltose binding protein outside of and in GroEL
TLDR
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As ribosomes initiate synthesis of a polypeptide chain, its precise folding into the functional three-dimensional protein structure is achieved either by spontaneous self-folding or byExpand
Efficient Catalysis of Protein Folding by GroEL/ES of the Obligate Chaperonin Substrate MetF.
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Analysis of spontaneous and chaperonin-assisted folding of the essential enzyme 5,10-methylenetetrahydrofolate reductase (MetF) of E. coli reveals a remarkable capacity of GroEL/ES to catalyze folding of an endogenous substrate protein that would have co-evolved with the chaper onin system. Expand
Molecular chaperones maximize the native state yield on biological times by driving substrates out of equilibrium
TLDR
A minimal stochastic model based on the Iterative Annealing Mechanism is proposed that satisfies the expectation that proteins and RNA be folded by chaperones on biologically relevant time scales, even if the final yield is lower than what equilibrium thermodynamics would dictate. Expand
GroEL actively stimulates folding of the endogenous substrate protein PepQ
TLDR
These findings strongly support an active model of chaperonin-mediated protein folding, where partial unfolding of misfolded intermediates plays a key role. Expand
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References

SHOWING 1-10 OF 144 REFERENCES
Essential role of the chaperonin folding compartment in vivo
TLDR
The GroEL/GroES compartment is essential for protein folding in vivo, as shown in vitro, and the observed acceleration of folding was dependent on protein encapsulation by GroES but independent of GroES cycling regulated by the GroEL ATPase. Expand
Catalysis of protein folding by symmetric chaperone complexes.
TLDR
It is demonstrated that the GroE proteins efficiently catalyze the folding of kinetically trapped folding intermediates of a mutant of maltose-binding protein (MBP Y283D) in an ATP-dependent way. Expand
Dual Function of Protein Confinement in Chaperonin-Assisted Protein Folding
TLDR
It is shown that the cage formed by GroEL and its cofactor GroES can have a dual role in promoting folding, and confinement of unfolded protein in the narrow hydrophilic space of the chaperonin cage smoothes the energy landscape for the folding of some proteins. Expand
Monitoring Protein Conformation along the Pathway of Chaperonin-Assisted Folding
TLDR
It is found that DnaK/DnaJ stabilizes the protein in collapsed states that fold exceedingly slowly, and segmental chain release and compaction may be important in avoiding misfolding by proteins that fail to fold efficiently through spontaneous hydrophobic collapse. Expand
Proteome-wide Analysis of Chaperonin-Dependent Protein Folding in Escherichia coli
TLDR
It is suggested that the chaperonin system may have facilitated the evolution of this fold into a versatile platform for the implementation of numerous enzymatic functions. Expand
How protein thermodynamics and folding mechanisms are altered by the chaperonin cage: Molecular simulations
  • F. Takagi, N. Koga, S. Takada
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
In kinetic study, the folding is accelerated in a modestly well confined case, which is consistent with a recent experimental result on ribulose-1,5-bisphosphate carboxylase-oxygenase folding and simulation results of a β hairpin. Expand
Effects of confinement in chaperonin assisted protein folding: rate enhancement by decreasing the roughness of the folding energy landscape.
TLDR
The role of confinement in chaperonin mediated folding is investigated through molecular dynamics simulations, designed a substrate protein with an alpha/beta sandwich fold and confined it to a spherical hydrophilic cage which mimicked the interior of the GroEL/ES cavity. Expand
Structural Features of the GroEL-GroES Nano-Cage Required for Rapid Folding of Encapsulated Protein
TLDR
It is suggested that by combining these features, the chaperonin cage provides a physical environment optimized to catalyze the structural annealing of proteins with kinetically complex folding pathways. Expand
Location of a folding protein and shape changes in GroEL–GroES complexes imaged by cryo-electron microscopy
TLDR
The first direct visualization, by cryo-electron microscopy, of a non-native protein substrate (malate dehydrogenase) bound to the mobile, outer domains at one end of GroEL is reported. Expand
Expansion and compression of a protein folding intermediate by GroEL.
TLDR
It is shown that denatured RuBisCO from Rhodospirillum rubrum populates a stable, nonaggregating, and kinetically trapped monomeric state at low temperature. Expand
...
1
2
3
4
5
...