The IbpA and IbpB small heat-shock proteins are substrates of the AAA+ Lon protease

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Molecular Microbiology (Impact Factor: 4.42). 02/2010; 75(6):1539-49. DOI: 10.1111/j.1365-2958.2010.07070.x
Source: PubMed


Small heat-shock proteins (sHSPs) are a widely conserved family of molecular chaperones, all containing a conserved alpha-crystallin domain flanked by variable N- and C-terminal tails. We report that IbpA and IbpB, the sHSPs of Escherichia coli, are substrates for the AAA+ Lon protease. This ATP-fueled enzyme degraded purified IbpA substantially more slowly than purified IbpB, and we demonstrate that this disparity is a consequence of differences in maximal Lon degradation rates and not in substrate affinity. Interestingly, however, IbpB stimulated Lon degradation of IbpA both in vitro and in vivo. Furthermore, although the variable N- and C-terminal tails of the Ibps were dispensable for proteolytic recognition, these tails contain critical determinants that control the maximal rate of Lon degradation. Finally, we show that E. coli Lon degrades variants of human alpha-crystallin, indicating that Lon recognizes conserved determinants in the folded alpha-crystallin domain itself. These results suggest a novel mode for Lon substrate recognition and provide a highly suggestive link between the degradation and sHSP branches of the protein quality-control network.

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    • "Nevertheless, slight improvements in production efficiencies were observed upon the deletion of lon and hflK gene across all culturing and heating conditions. Improvements in LCC DNA production for Δlon derivatives were speculated to be attributed to diminished degradation of small heat shock proteins, IbpA and IbpB, by Lon protease [41]. IbpA and IbpB are holding chaperones that intercalated into protein aggregates and stabilize folding intermediates for folding chaperones [31], [34], [38]. "
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