ABSTRACT
ALEXANDER BUCHBERGER1, JOCHEN REINSTEIN2 and BERND BUKAU3, *
1 Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK
2 Abteilung Physikalische Biochemie, Max Planck-Institut für Molekulare Physiologie, Rheinlanddamm 201, D-44139 Dortmund, Germany
3 Institut für Biochemie und Molekularbiologie, Universität Freiburg, HermannHerder-Str. 7, D-79104 Freiburg, Germany
* Corresponding author
1. Introduction 2. Components of the DnaK Chaperone System 2.1. DnaK 2.1.1. Structure 2.1.2. Substrate Binding and its Coupling to the Nucleotide Status of DnaK 2.2. DnaJ 2.2.1. Structure 2.2.2. Structural Basis for the Interaction with DnaK 2.2.3. Substrate Binding 2.3. GrpE 3. The ATPase Cycle of DnaK 3.1. Binding of ATP 3.2. Switch 1: ATP Hydrolysis and the Role of DnaJ 3.3. Switch 2: Product Release and the Role of GrpE 3.4. Balance of Rate Constants 4. The Chaperone Cycle 5. Other Hsp70 Systems 6. Perspectives 7. Acknowledgements 8. References
1. INTRODUCTION
The ubiquitous Hsp70 chaperones and their cofactors are central components of the cellular system for folding, repair and degradation of proteins. They cooperate with other chaperones to assist protein folding reactions in a large variety of metabolic processes in most cellular compartments. In this chaperone network, Hsp70 proteins have unique and essential functions which rely on their ability to associate with short hydrophobic segments of polypeptides in an ATP-dependent manner (Haiti, 1996; Rüdiger et al., 1997a). Such association can prevent aggregation of substrates, by shielding exposed hydrophobic segments of polypeptides, and assist refolding, probably by decreasing the concentration of aggregation-prone folding intermediates.
