Mechanism of Hsp104/ClpB inhibition by prion curing Guanidinium hydrochloride
The Saccharomyces cerevisiae AAA+ protein Hsp104 and its Escherichia coli counterpart ClpB cooperate with Hsp70 chaperones to refold aggregated proteins and fragment prion fibrils. Hsp104/ClpB activity is regulated by interaction of the M-domain with the first ATPase domain (AAA-1), controlling ATP...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
14 February 2013
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| In: |
FEBS letters
Year: 2013, Volume: 587, Issue: 6, Pages: 810-817 |
| ISSN: | 1873-3468 |
| DOI: | 10.1016/j.febslet.2013.02.011 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.febslet.2013.02.011 Verlag, lizenzpflichtig, Volltext: https://febs.onlinelibrary.wiley.com/doi/abs/10.1016/j.febslet.2013.02.011 
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| Author Notes: | Eva Kummer, Yuki Oguchi, Fabian Seyffer, Bernd Bukau, Axel Mogk |
| Summary: | The Saccharomyces cerevisiae AAA+ protein Hsp104 and its Escherichia coli counterpart ClpB cooperate with Hsp70 chaperones to refold aggregated proteins and fragment prion fibrils. Hsp104/ClpB activity is regulated by interaction of the M-domain with the first ATPase domain (AAA-1), controlling ATP turnover and Hsp70 cooperation. Guanidinium hydrochloride (GdnHCl) inhibits Hsp104/ClpB activity, leading to prion curing. We show that GdnHCl binding exerts dual effects on Hsp104/ClpB. First, GdnHCl strengthens M-domain/AAA-1 interaction, stabilizing Hsp104/ClpB in a repressed conformation and abrogating Hsp70 cooperation. Second, GdnHCl inhibits continuous ATP turnover by AAA-1. These findings provide the mechanistic basis for prion curing by GdnHCl. |
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| Item Description: | Gesehen am 30.06.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1873-3468 |
| DOI: | 10.1016/j.febslet.2013.02.011 |