Hsp 104 , Hsp 70 , and Hsp 40 : A Novel Chaperone System that Rescues Previously Aggregated
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چکیده
are involved in protein turnover. Neither ClpA nor ClpX Hsp104 is a stress tolerance factor that promotes the has intrinsic proteolytic activity. Rather, both proteins reactivation of heat-damaged proteins in yeast by an confer ATP-dependent turnover of their substrates unknown mechanism. Herein, we demonstrate that through a physical association with an unrelated oligoHsp104 functions in this process directly. Unlike other meric protease ClpP (Katayama-Fujimura et al., 1987; chaperones, Hsp104 does not prevent the aggregation Hwang et al., 1988; Wojtkowiak et al., 1993). In the abof denatured proteins. However, in concert with Hsp40 sence of this protease partner protein, ClpA disassemand Hsp70, Hsp104 can reactivate proteins that have bles inactive RepA dimers, releasing active monomers been denatured and allowed to aggregate, substrates (Wickner et al., 1994; Pak and Wickner, 1997), and ClpX refractory to the action of other chaperones. Hsp104 disassembles the MuA tetramer/DNA complex, releascooperates with the chaperones present in reticuloing free functional MuA monomers (Levchenko et al., cyte lysates but not with DnaK of E. coli. We conclude 1995). Hsp104 hasno detectable role in protein degradathat Hsp104 has a protein remodeling activity that acts tion (Parsell et al., 1993), but structural conservation on trapped, aggregated proteins and requires specific among the HSP100s suggests that all family members interactions with conventional chaperones to promote may employ a common molecular mechanism with disrefolding of the intermediates it produces. tinct consequences. Thus, Hsp104 may also act by pull-
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