Protein folding in the central cavity of the GroEL–GroES chaperonin complex

@article{Mayhew1996ProteinFI,
  title={Protein folding in the central cavity of the GroEL–GroES chaperonin complex},
  author={M. Mayhew and Ana C. R. da Silva and J{\"o}rg Martin and H. Erdjument-Bromage and P. Tempst and F. Hartl},
  journal={Nature},
  year={1996},
  volume={379},
  pages={420-426}
}
The chaperonin GroEL is able to mediate protein folding in its central cavity. GroEL-bound dihydrofolate reductase assumes its native conformation when the GroES cofactor caps one end of the GroEL cylinder, thereby discharging the unfolded polypeptide into an enclosed cage. Folded dihydrofolate reductase emerges upon ATP-dependent GroES release. Other proteins, such as rhodanese, may leave GroEL after having attained a conformation that is committed to fold. Incompletely folded polypeptide… Expand
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The models of GroEL-assisted protein folding assuming ligand-controlled dissociation of nonnative proteins from the GroEL surface and their folding in the bulk solution are discussed. Expand
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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
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TLDR
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TLDR
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TLDR
Structures of gp23–chaperonin complexes are presented, showing both the initial captured state and the final, close-to-native state with gp23 encapsulated in the folding chamber, explaining why the GroEL–GroES complex is not able to fold gp23 and showing how the chaperon in structure distorts to enclose a large, physiological substrate protein. Expand
The crystal structure of the asymmetric GroEL–GroES–(ADP)7 chaperonin complex
TLDR
The structure of the GroEL–GroES–(ADP)7 complex reveals how large en bloc movements of the cis ring's intermediate and apical domains enable bound GroES to stabilize a folding chamber with ADP confined to the cisRing, suggesting a model for an ATP-driven folding cycle that requires a double toroid. Expand
The oligomeric structure of GroEL/GroES is required for biologically significant chaperonin function in protein folding
TLDR
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Flexibility of GroES mobile loop is required for efficient chaperonin function.
TLDR
It is shown that restriction of the flexibility of the loop by a disulfide cross-linking between cysteines within the loop results in the inefficient formation of a stable GroEL-polypeptide-GroES ternary complex and inefficient folding. Expand
Visualizing GroEL/ES in the Act of Encapsulating a Folding Protein
TLDR
Using symmetry-free, single-particle cryo-electron microscopy, a chemically modified mutant of GroEL (EL43Py) is characterized that is trapped at a normally transient stage of substrate protein encapsulation. Expand
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References

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TLDR
The reaction mechanism of protein folding by the chaperonin GroEL and its regulator GroES has been defined and partially folded protein rebinds to the chacheronin, thus perpetuating the cycle until folding is complete. Expand
Functional significance of symmetrical versus asymmetrical GroEL-GroES chaperonin complexes
TLDR
Electron microscopic and biochemical analyses have now shown that unphysiologically high magnesium concentrations and increased pH are required to assemble symmetrical complexes, the formation of which precludes the association of unfolded polypeptide. Expand
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TLDR
Folding of two monomeric enzymes mediated by groE has been reconstituted in vitro and might represent a general mechanism for the formation of protein structure in vivo. Expand
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TLDR
The functional chaperonin unit is an asymmetrical GroEL:GroES complex, and substrate protein plays an active role in modulating the chaper onin reaction cycle. Expand
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TLDR
These results suggest a mechanism for the GroEL-mediated folding of rhodanese in which the domain-forming regions of the polypeptide are kept apart and are then released, perhaps sequentially, resulting in correct folding. Expand
ATP induces non-identity of two rings in chaperonin GroEL.
TLDR
It is suggested that interaction with ATP induces structural and functional differences between two initially identical rings in GroEL (inter-ring negative cooperativity) and that the subsequent binding of GroES occurs to the ring that is occupied first by ATP in a positively cooperative manner. Expand
Chaperonin‐mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity.
TLDR
The functional complex of GroEL and GroES is characterized by asymmetrical binding of GroES to one end of the GroEL cylinder and it is suggested that binding of the substrate protein occurs within the central cavity ofGroEL. Expand
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TLDR
A mutational analysis is undertaken that relates the functional prop-erties of GroEL to its crystal structure and finds a highly conserved residue, Asp 87, positioned within a putative nucleotide-binding pocket in the top of the equatorial domain, is essential for ATP hydrolysis and polypeptide release. Expand
Destabilization of the complete protein secondary structure on binding to the chaperone GroEL
TLDR
Nuclear magnetic resonance techniques are used to show that the interaction of the small protein cyclophilin with GroEL is reversible by temperature changes, and all amide protons in GroEL-bound cyclophillin are exchanged with the solvent, although this exchange does not occur in free cyclophILin. Expand
(Mg–ATP)-dependent self-assembly of molecular chaperone GroEL
TLDR
The (Mg–ATP)-dependent self-stimulation ('self-chaperoning') in vitro of GroELp reassembly from its monomeric state is shown. Expand
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