The heat shock protein LarA activates the Lon protease in response to proteotoxic stress.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 Nov 2023
22 Nov 2023
Historique:
received:
08
08
2023
accepted:
07
11
2023
medline:
24
11
2023
pubmed:
23
11
2023
entrez:
22
11
2023
Statut:
epublish
Résumé
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 high levels of LarA cause growth inhibition in a Lon-dependent manner and that Lon-mediated degradation of LarA itself ensures low LarA levels in the absence of stress. We suggest that the temporal LarA-dependent activation of Lon helps to meet an increased proteolysis demand in response to 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.
Identifiants
pubmed: 37993443
doi: 10.1038/s41467-023-43385-x
pii: 10.1038/s41467-023-43385-x
pmc: PMC10665427
doi:
Substances chimiques
Protease La
EC 3.4.21.53
Heat-Shock Proteins
0
Escherichia coli Proteins
0
Endopeptidases
EC 3.4.-
ATP-Dependent Proteases
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7636Subventions
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2016-03300
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2019-01961
Organisme : Stiftelsen för Strategisk Forskning (Swedish Foundation for Strategic Research)
ID : FFL15-0005
Organisme : Stockholms Universitet (Stockholm University)
ID : SFO program
Informations de copyright
© 2023. The Author(s).
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