Heat activates the AAA+ HslUV protease by melting an axial autoinhibitory plug

• Authors: Vladimir Baytshtok, Massachusetts Institute of Technology; Xue Fei, Massachusetts Institute of Technology; Tsai-Ting Shih, Massachusetts Institute of Technology; Robert A Grant, Massachusetts Institute of Technology; Justin C Santos, Emory University; Tania A Baker, Massachusetts Institute of Technology; Robert T Sauer, Massachusetts Institute of Technology
• Journal Title: Cell Reports
• Volume: Volume 34, Number 3
• Publisher: Elsevier | 2021-01-19
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.celrep.2020.108639
• Subjects: Health Sciences, Oncology; Health Sciences, Medicine and Surgery
• Keywords: Heat

Abstract

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.