Clp ATPase

Clp ATPases AND THEIR ROLE IN PROTEIN UNFOLDING AND DEGRADATION... 

III. Chaperone Activity of Clp ATPases and Their Participation in Proteolysis. . 415... 

IV. Structure of Clp ATPases Alone and with Partner Proteases. 416... 

Fig. 1. Schematic representation of the domain structures of different classes of Clp ATPases.

Clp ATPases and their role in protein unfolding and degradation 415... 

The crystal structure of one Clp ATPase, HslU, has been solved alone and in a complex with its proteolytic component, HslV (Bochtler et al., 2000 Sousa et al., 2000) (Fig. 3, see color insert). The E. coli HslU... 

Several mechanistic aspects regarding the chaperone activity of Clp ATPases and their role in proteolysis have emerged from these structural studies (1) The active sites of the protease are sequestered from the cytoplasm and thus are not in a position to degrade most cellular... 

Clp ATPases AND THEIR ROLE in protein unfolding and degradation 419... 

V. Mechanism of Action of Clp ATPases as Chaperones and as Components of Degradation Machinery... 

Specific substrates bound to Clp ATPases have been visualized by electron microscopy. ClpAP and ClpXP bind RepA and XO, respectively, at... 

Protein unfolding is very likely a general mechanism used by Clp ATPases to carry out their other biological roles in addition to translocation of substrates to proteases. Although it is not a prerequisite that a protein be globally unfolded to be remodeled, very likely RepA dimers,... 

These examples of specificity factors involved in modulating the recognition specificity of Clp ATPases point out the existence of yet another level of regulation of degradation to assure accurate degradation of... 

Although much has been learned about the structure and function of Clp chaperones and their role in proteolysis, the mechanism of protein unfolding catalyzed by Clp ATPases and the mechanism of translocation of the unfolded proteins from Clp ATPases to partner proteases remain unsolved puzzles. However, models in which mechanical force is used to destabilize the structure of the substrate in a processive and directional manner are probable. It also seems likely that when ClpA ATPases are associated with proteases, unfolding is coupled to extrusion of the unfolded protein into the proteolytic cavity. In summary, it is anticipated that the large family of Clp ATPases will accomplish their many important cellular functions by similar mechanisms and what has been learned by studying the prokaryotic members reviewed here will shed a great deal of light on all members of the family. 

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