Abstract
ClpB of E. coli and yeast Hsp104 are homologous molecular chaperones and members of the AAA+ (ATPases Associated with various cellular Activities) superfamily of ATPases. They are required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions. ClpB and Hsp104 collaborate with the DnaK or Hsp70 chaperone system, respectively, to dissolve protein aggregates both in vivo and in vitro. In yeast, the propagation of prions depends upon Hsp104. Since protein aggregation and amyloid formation are associated with many diseases, including neurodegenerative diseases and cancer, understanding how disaggregases function is important. In this study, we have explored the innate substrate preferences of ClpB and Hsp104 in the absence of the DnaK and Hsp70 chaperone system. The results suggest that substrate specificity is determined by nucleotide binding domain-1.
Highlights
All cells have a protein network involved in maintaining the proteome following periods of stress
The experiments addressing this question were performed in the absence of the DnaK or Hsp70 chaperone so it would be possible to study the basic properties of the ClpB/Hsp104 machine and avoid the complication of substrate recognition by DnaK and Hsp70
We showed that Hsp104 and ClpB, in the absence of Hsp70 or DnaK, exhibit differing substrate preferences
Summary
All cells have a protein network involved in maintaining the proteome following periods of stress. Hsp104 and ClpB are two members of the Clp/Hsp100 family and are found in yeast and bacteria, respectively, where they are essential for growth following extreme stress, such as high temperature (Hodson et al, 2012; Doyle et al, 2013; Mogk et al, 2015) They aid in cell survival by disaggregating and reactivating proteins inactivated and aggregated following stress conditions (Hodson et al, 2012; Doyle et al, 2013; Mogk et al, 2015). Protein disaggregation and reactivation by Hsp104/ClpB require the collaboration of another molecular chaperone, Hsp70/DnaK and its cochaperones (Glover and Lindquist, 1998; Goloubinoff et al, 1999; Motohashi et al, 1999; Zolkiewski, 1999)
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