Cell Reports
Volume 34, Issue 3, 19 January 2021, 108639
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Report
Heat activates the AAA+ HslUV protease by melting an axial autoinhibitory plug

https://doi.org/10.1016/j.celrep.2020.108639Get rights and content
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Highlights

  • A trimeric structure can plug the axial channel of the AAA+ HslU ring hexamer

  • This autoinhibitory plug is observed in crystal structures and by electron microscopy

  • Temperature-induced melting of the plug activates ATP hydrolysis and proteolysis

  • Low-temperature autoinhibition limits rogue degradation after recovery from heat shock

Summary

At low temperatures, protein degradation by the AAA+ HslUV protease is very slow. New crystal structures reveal that residues in the intermediate domain of the HslU6 unfoldase can plug its axial channel, blocking productive substrate binding and subsequent unfolding, translocation, and degradation by the HslV12 peptidase. Biochemical experiments with wild-type and mutant enzymes support a model in which heat-induced melting of this autoinhibitory plug activates HslUV proteolysis.

Keywords

temperature control
ATP-dependent degradation
proteolytic regulation
heat shock locus

Cited by (0)

2

These authors contributed equally

3

Senior author

4

Present address: Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

5

MD/PhD Program, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA

6

Lead Contact