Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine.

Détails

ID Serval
serval:BIB_0B7396479C9A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine.
Périodique
Nature communications
Auteur(s)
Mazal H., Iljina M., Barak Y., Elad N., Rosenzweig R., Goloubinoff P., Riven I., Haran G.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
29/03/2019
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
1438
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Large protein machines are tightly regulated through allosteric communication channels. Here we demonstrate the involvement of ultrafast conformational dynamics in allosteric regulation of ClpB, a hexameric AAA+ machine that rescues aggregated proteins. Each subunit of ClpB contains a unique coiled-coil structure, the middle domain (M domain), proposed as a control element that binds the co-chaperone DnaK. Using single-molecule FRET spectroscopy, we probe the M domain during the chaperone cycle and find it to jump on the microsecond time scale between two states, whose structures are determined. The M-domain jumps are much faster than the overall activity of ClpB, making it an effectively continuous, tunable switch. Indeed, a series of allosteric interactions are found to modulate the dynamics, including binding of nucleotides, DnaK and protein substrates. This mode of dynamic control enables fast cellular adaptation and may be a general mechanism for the regulation of cellular machineries.
Mots-clé
Allosteric Regulation, Binding Sites, Endopeptidase Clp/chemistry, Endopeptidase Clp/metabolism, Fluorescence Resonance Energy Transfer, HSP70 Heat-Shock Proteins/metabolism, Models, Molecular, Protein Aggregates, Protein Domains, Substrate Specificity, Thermus thermophilus/enzymology, Time Factors
Pubmed
Web of science
Création de la notice
15/04/2019 10:01
Dernière modification de la notice
21/08/2019 6:36
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