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

  title={Protein folding in the central cavity of the GroEL–GroES chaperonin complex},
  author={Mark W. Mayhew and Ana C. R. da Silva and J{\"o}rg Martin and Hediye Erdjument-Bromage and Paul Tempst and F. Ulrich Hartl},
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… 

GroEL-Assisted Protein Folding: Does It Occur Within the Chaperonin Inner Cavity?

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.

Structure and function in GroEL-mediated protein folding.

Major, asymmetric conformational changes in the GroEL double toroid accompany binding of ATP and the cochaperonin GroES to form a cis ternary complex, which allows the polypeptide to achieve its final native state, if folding was completed, or to recycle to another chaper onin molecule, if the folding process did not result in a form committed to the native state.

GroEL stimulates protein folding through forced unfolding

It is demonstrated that unfolding of a substrate protein by GroEL enhances protein folding, and forced protein unfolding is a central component of the multilayered stimulatory mechanism used byGroEL to drive protein folding.

Chaperonin complex with a newly folded protein encapsulated in the folding chamber

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.

The crystal structure of the asymmetric GroEL–GroES–(ADP)7 chaperonin complex

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.

The oligomeric structure of GroEL/GroES is required for biologically significant chaperonin function in protein folding

It is shown that the apical domain binds aggregation-sensitive polypeptides but cannot significantly assist their refolding in vitro and fails to replace the groEL gene or to complement defects of groEL mutants in vivo, suggesting sequestration of aggregation-prone intermediates in a folding cage is an important element of the chaperonin mechanism.

Visualizing GroEL/ES in the Act of Encapsulating a Folding Protein




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

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.

Functional significance of symmetrical versus asymmetrical GroEL-GroES chaperonin complexes

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.

Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate

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.

Asymmetrical interaction of GroEL and GroES in the ATPase cycle of assisted protein folding

The functional chaperonin unit is an asymmetrical GroEL:GroES complex, and substrate protein plays an active role in modulating the chaper onin reaction cycle.

Binding of defined regions of a polypeptide to GroEL and its implications for chaperonin-mediated protein folding

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.

Chaperonin‐mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity.

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.

Residues in chaperonin GroEL required for polypeptide binding and release

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.

Destabilization of the complete protein secondary structure on binding to the chaperone GroEL

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.

(Mg–ATP)-dependent self-assembly of molecular chaperone GroEL

The (Mg–ATP)-dependent self-stimulation ('self-chaperoning') in vitro of GroELp reassembly from its monomeric state is shown.