ABSTRACT

Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK

1Present address: Department of Crystallography, Birkbeck College London, Malet Street, London, WC1E 7HX, UK

1. Introduction 2. GroEL-protein Interactions: Some Basic Considerations 3. ATP-induced Rearrangements 3.1. Equilibrium Properties and Transient Kinetics of the ATP-induced Conformational Switch

3.2. Negative Co-operativity and the Establishment of Asymmetry in the GroEL Toroids 4. The Binding of ADP 4.1. Weak and Tight Interactions-A Further Manifestation of Negative Co-operativity 5. The GroEL ATPase Cycle in the Absence of GroES 6. GroES-GroEL Interactions and Their Effects on the Hydrolysis of ATP 6.1. Binding of GroES to the ADP and ATP States of GroEL 6.2. ATP Hydrolysis in the Presence of GroES 6.3. The Dissociation of GroES During the ATPase Cycle 6.4. Bullets and Footballs 7. The Coupling of Protein and Nucleotide Binding Affinities 7.1. The Effects of ATP, ADP & AMP-PNP on Protein Binding Affinity 7.2. The Effect of Unfolded Protein on Co-operativity Within the GroEL Oligomer 8. The Coupling of the ATPase Cycle to Chaperonin-assisted Protein Folding 8.1. Models of Chaperonin Action 8.1.1. Encapsulation and Folding 8.1.2. Unfolding and Release 8.2. Towards a Global Model for GroE-mediated Folding 9. Concluding Remarks 10. Acknowledgements

11. References

Abbreviations

*Corresponding author

1. INTRODUCTION

One of the central tenets of biogenesis is that the primary sequence of a protein contains all of the information necessary to specify the precise, three-dimensional structure of the native state. At its simplest, protein folding can be viewed as a directed conformational search which locates the kinetically accessible state of lowest free energy. Given that the principle function of the GroE proteins is to enhance the efficiency of the folding process, it is somewhat curious that energy derived from ATP hydrolysis is required to facilitate a reaction which is intrinsically thermodynamically favourable. Where does this chemically derived energy go and how is it harnessed?