The heat shock protein LarA activates the Lon protease at the onset of proteotoxic stress

• The Lon protease is a highly conserved protein degradation machine that has critical regulatory and protein quality control functions in cells from the three domains of life. Here, we report the discovery of a α-proteobacterial heat shock protein, LarA, that functions as a dedicated Lon regulator. We show that LarA accumulates at the onset of proteotoxic stress and allosterically activates Lon-catalysed degradation of a large group of substrates through a five amino acid sequence at its C-terminus. Further, we find that LarA is regulated by Lon itself, which is critical to prevent toxic overactivation of Lon. We suggest that the temporal LarA-dependent activation of Lon helps to meet an increased proteolysis demand at the onset of protein unfolding stress. Our study defines a regulatory interaction of a conserved protease with a heat shock protein, serving as a paradigm of how protease activity can be tuned under changing environmental conditions.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

proteolysis

protein quality control

allosteric regulation

bacteria

heat shock response

AAA+ protease

molekylär biovetenskap

Molecular Bioscience

molekylärbiologi

Molecular Biology

mikrobiologi

Microbiology

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)