Chaperonin-mediated protein folding: fate of substrate polypeptide

  title={Chaperonin-mediated protein folding: fate of substrate polypeptide},
  author={Wayne A. Fenton and Arthur L. Horwich},
  journal={Quarterly Reviews of Biophysics},
  pages={229 - 256}
1. Chaperonin action – an overview 230 2. Polypeptide binding – an essential action 235 3. Recognition of non-native polypeptide – role of hydrophobicity 236 4. Crystallographic analyses of peptide binding 237 5. Topology and secondary and tertiary structure of bound substrate polypeptide – fluorescence, hydrogen exchange and NMR studies 239 6. Binding by GroEL associated with a putative unfolding action 242 7. A potential action of substrate unfolding driven by ATP/GroES binding 245 8. Folding… 
Chaperonin-mediated protein folding: using a central cavity to kinetically assist polypeptide chain folding
It is concluded that GroEL, in general, behaves passively with respect to its substrate proteins during these steps, and chamber-mediated folding appears to resemble folding in solution, except that major kinetic complications of multimolecular association are prevented.
Chaperonin-mediated folding of viral proteins.
The phiEL chaper onin from phage EL is revealed to be the first virally encoded chaperonin and is proposed to function independently of the host chaperOnin machinery.
GroEL-Mediated Protein Folding: Making the Impossible, Possible
  • Zong Lin, H. Rye
  • Biology
    Critical reviews in biochemistry and molecular biology
  • 2006
Some of the general properties of proteins that do not fold well in the absence of GroEL are examined and then how folding of these proteins is enhanced by GroEL and GroES are considered.
Active Cage Mechanism of Chaperonin-Assisted Protein Folding Demonstrated at Single-Molecule Level
Findings suggest that protein encapsulation can accelerate folding by entropically destabilizing folding intermediates, in strong support of an active chaperonin mechanism in the folding of some proteins.
Functional Subunits of Eukaryotic Chaperonin CCT/TRiC in Protein Folding
The eukaryotic chaperonin CCT is a large, multisubunit, cylindrical structure having two identical rings stacked back to back and it has a built-in lid structure responsible for closing the central cavity.
Chaperonin-co-chaperonin interactions.
A greater understanding of the fascinating roles of both intracellular and extracellular Hsp10, in addition to its role as a co-chaper onin, on cellular processes will accelerate the development of techniques to treat diseases associated with the chaperonin family.
Action of the chaperonin GroEL/ES on a non-native substrate observed with single-molecule FRET.
Two families of chaperonin: physiology and mechanism.
A number of issues under current study are discussed, including the range of substrates acted on by the two classes of chaperonin, in particular by GroEL in the bacterial cytoplasm and CCT in the eukaryotic cytosol, and are all these substrates subject to encapsulation.


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.
Basis of substrate binding by the chaperonin GroEL.
The molecular basis of GroEL-substrate recognition is the presentation of a hydrophobic surface by an incompletely folded polypeptide and that many backbone conformations can be accommodated.
The chaperonin GroEL binds a polypeptide in an alpha-helical conformation.
It is proposed that GroEL interacts with sequences in an incompletely folded chain that have the potential to adopt an amphipathic alpha-helix and that the chaperonin binding site promotes formation of a helix.
Native-like structure of a protein-folding intermediate bound to the chaperonin GroEL.
It is concluded that significant native-like structure is present in protein-folding intermediates bound to GroEL, and the pattern and magnitude of amide proton protection indicate that the central parallel beta-sheet found in native DHFR is presentIn a moderately stable state in GroEL-bound DHFR.
GroEL Binds to and Unfolds Rhodanese Posttranslationally (*)
GroEL is able to assist in the folding of newly synthesized proteins following release from the ribosome and that GroEL can unfold a trapped protein folding intermediate of rhodanese.
The Hydrophobic Nature of GroEL-Substrate Binding (*)
The negative heat capacity change provides strong evidence for the role of hydrophobic interactions as the driving force for the association of these substrates with the GroEL chaperonin.
Toward a mechanism for GroEL.GroES chaperone activity: an ATPase-gated and -pulsed folding and annealing cage.
  • F. Corrales, A. Fersht
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
Free GroEL binds denatured proteins very tightly: it retards the folding of barnase 400-fold and catalyzes unfolding fluctuations in native barnase and its folding intermediate and is the gatekeeper that selects for initial entry of slow-folding proteins to the chaperone action and then pumps successive transitions from the faster- folding R-states to the tighter-binding/stronger annealing T-states.
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.