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

Vladimir Baytshtok; Xue Fei; Tsai-Ting Shih; Robert A Grant; Justin C Santos; Tania A Baker; Robert T Sauer

doi:10.1016/j.celrep.2020.108639

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

Cell Rep. 2021 Jan 19;34(3):108639. doi: 10.1016/j.celrep.2020.108639.

Authors

Vladimir Baytshtok¹, Xue Fei¹, Tsai-Ting Shih¹, Robert A Grant¹, Justin C Santos¹, Tania A Baker¹, Robert T Sauer²

Affiliations

¹ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: bobsauer@mit.edu.

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.

Keywords: ATP-dependent degradation; heat shock locus; proteolytic regulation; temperature control.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

ATPases Associated with Diverse Cellular Activities / metabolism*
Hot Temperature

Substances

ATPases Associated with Diverse Cellular Activities

Abstract

Publication types

MeSH terms

Substances

Grants and funding