Towards a unifying mechanism for ClpB/Hsp104-mediated protein disaggregation and prion propagation
- PMID: 20130680
- DOI: 10.1139/o09-118
Towards a unifying mechanism for ClpB/Hsp104-mediated protein disaggregation and prion propagation
Abstract
The oligomeric AAA+ chaperones ClpB/Hsp104 mediate the reactivation of aggregated proteins, an activity that is crucial for the survival of cells during severe stress. Hsp104 is also essential for the propagation of yeast prions by severing prion fibres. Protein disaggregation depends on the cooperation of ClpB/Hsp104 with a cognate Hsp70 chaperone system. While Hsp70 chaperones are also involved in prion propagation, their precise role is much less well defined compared with its function in aggregate solubilization. Therefore, it remained unclear whether both ClpB/Hsp104 activities are based on common or different mechanisms. Novel data show that ClpB/Hsp104 uses a motor threading activity to remodel both protein aggregates and prion fibrils. Moreover, transfer of both types of substrates to the ClpB/Hsp104 processing pore site requires initial substrate interaction of Hsp70. Together these data emphasize the similarity of thermotolerance and prion propagation pathways and point to a shared mechanistic principle of Hsp70-ClpB/Hsp104-mediated solubilization of amorphous and ordered aggregates.
Similar articles
-
Chaperone networks in protein disaggregation and prion propagation.J Struct Biol. 2012 Aug;179(2):152-60. doi: 10.1016/j.jsb.2012.05.002. Epub 2012 May 10. J Struct Biol. 2012. PMID: 22580344 Review.
-
Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation.Mol Microbiol. 2008 Apr;68(1):87-97. doi: 10.1111/j.1365-2958.2008.06135.x. Epub 2008 Feb 28. Mol Microbiol. 2008. PMID: 18312264
-
Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB.Cell. 2004 Nov 24;119(5):653-65. doi: 10.1016/j.cell.2004.11.027. Cell. 2004. PMID: 15550247
-
Novel insights into the mechanism of chaperone-assisted protein disaggregation.Biol Chem. 2005 Aug;386(8):739-44. doi: 10.1515/BC.2005.086. Biol Chem. 2005. PMID: 16201868 Review.
-
Bacterial and Yeast AAA+ Disaggregases ClpB and Hsp104 Operate through Conserved Mechanism Involving Cooperation with Hsp70.J Mol Biol. 2016 Oct 23;428(21):4378-4391. doi: 10.1016/j.jmb.2016.09.003. Epub 2016 Sep 9. J Mol Biol. 2016. PMID: 27616763
Cited by
-
Functionality of Class A and Class B J-protein co-chaperones with Hsp70.FEBS Lett. 2015 Sep 14;589(19 Pt B):2825-30. doi: 10.1016/j.febslet.2015.07.040. Epub 2015 Aug 3. FEBS Lett. 2015. PMID: 26247431 Free PMC article.
-
Species-specific collaboration of heat shock proteins (Hsp) 70 and 100 in thermotolerance and protein disaggregation.Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6915-20. doi: 10.1073/pnas.1102828108. Epub 2011 Apr 7. Proc Natl Acad Sci U S A. 2011. PMID: 21474779 Free PMC article.
-
Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor.Proc Natl Acad Sci U S A. 2013 May 21;110(21):8513-8. doi: 10.1073/pnas.1217988110. Epub 2013 May 6. Proc Natl Acad Sci U S A. 2013. PMID: 23650362 Free PMC article.
-
Heterologous gln/asn-rich proteins impede the propagation of yeast prions by altering chaperone availability.PLoS Genet. 2013;9(1):e1003236. doi: 10.1371/journal.pgen.1003236. Epub 2013 Jan 24. PLoS Genet. 2013. PMID: 23358669 Free PMC article.
-
The Paf1 complex subunit Rtf1 buffers cells against the toxic effects of [PSI+] and defects in Rkr1-dependent protein quality control in Saccharomyces cerevisiae.Genetics. 2012 Aug;191(4):1107-18. doi: 10.1534/genetics.112.141713. Epub 2012 May 17. Genetics. 2012. PMID: 22595241 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
