DOI: 10.1111/j.1365-2958.2008.06135.x. Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation

Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation

10.1111/j.1365-2958.2008.06135.x

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

SummaryThe oligomeric AAA+ chaperone Hsp104 is essential for thermotolerance development and prion propagation in yeast. Thermotolerance relies on the ability of Hsp104 to cooperate with the Hsp70 chaperone system in the reactivation of heat‐aggregated proteins. Prion propagation requires the Hsp104‐dependent fragmentation of prion fibrils to create infectious seeds. It remained elusive whether both processes rely on common or different activities of Hsp104. Specifically, protein reactivation has been suggested to require a substrate threading activity of Hsp104 whereas fibril fragmentation may be mediated by a crowbar activity. Here we engineered an Hsp104 variant, HAP, which cooperates with the bacterial peptidase ClpP to form a novel proteolytic system. HAP threads aggregated model substrates as well as the yeast prion Sup35 through its central pore into associated ClpP. HAP variants that harbour a reduced threading activity were affected in both protein disaggregation and prion propagation, demonstrating that substrate threading represents the common mechanism for the processing of both substrate classes.

Bibliography

Tessarz, P., Mogk, A., & Bukau, B. (2008). Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation. Molecular Microbiology, 68(1), 87â97. Portico.

Authors 3

Peter Tessarz (first)
Axel Mogk (additional)
Bernd Bukau (additional)

References 35 Referenced 159

Dates

Type	When
Created	17 years, 6 months ago (Feb. 28, 2008, 5:29 a.m.)
Deposited	1 year, 11 months ago (Sept. 28, 2023, 10:21 p.m.)
Indexed	3 days, 11 hours ago (Sept. 3, 2025, 6 a.m.)
Issued	17 years, 6 months ago (Feb. 28, 2008)
Published	17 years, 6 months ago (Feb. 28, 2008)
Published Online	17 years, 6 months ago (Feb. 28, 2008)
Published Print	17 years, 5 months ago (April 1, 2008)

Funders 0

None

BibTeX

@article{Tessarz_2008, title={Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation}, volume={68}, ISSN={1365-2958}, url={http://dx.doi.org/10.1111/j.1365-2958.2008.06135.x}, DOI={10.1111/j.1365-2958.2008.06135.x}, number={1}, journal={Molecular Microbiology}, publisher={Wiley}, author={Tessarz, Peter and Mogk, Axel and Bukau, Bernd}, year={2008}, month=feb, pages={87–97} }

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