Researchers at the Max Planck Institute for Biochemistry in Martinsried/Germany found that the cage structure of the chaperonin GroEL is essential for cellular protein folding (Nature Structural Biology, Vol. 5, Number 11, November 1998). Enclosure of an unfolded protein in the cage provided by the oligomeric GroEL protein efficiently prevents protein aggregation during folding. This is particularly critical for aggregation sensitive proteins (the bad guys) that expose significant hydrophobic surfaces to the solvent. In contrast to earlier proposals, repeated unfolding of partially folded polypeptides is not an essential part of this mechanism.
In the November issue of Nature Structural Biology (page 977-985), the authors Frank Weber, Manjit Hayer-Hartl and Franz-Ulrich Hartl report a study showing that "The oligomeric structure of GroEL-GroES is required for biologically significant chaperonin function in protein folding". This study includes in vivo complementation studies performed by the co-authors France Keppel and Costa Georgopoulos from the University of Geneva, Centre Medical Universitaire (Switzerland).
Chaperonins have been found in all cells investigated to date including
organelles like mitochondria and chloroplasts. The Escherichia coli chaperonin
GroEL is encoded by an essential gene and consists of 14 identical subunits.
These subunits are arranged in two heptameric rings which are stacked
back-to-back. Each ring encloses a central cavity in which substrate polypeptide
is bound by interaction with the apical domains of the GroEL monomers, which
form the opening of the cylinder. After substrate is bound inside the cavity,
GroES, a dome-shaped heptameric complex, closes the opening of the ring and
causes the release of unfolded substrate polypeptide into the central cavity. In
this enclosed environment, the substrate can fold to its native state. It is
subsequently released into the cytosol upon ATP-dependent dissociation of GroES
Contact: Franz-Ulrich Hartl