Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Science Advances Année : 2018

Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle

Résumé

Chaperonins are ubiquitous protein assemblies present in bacteria, eukaryota, and archaea, facilitating the folding of proteins, preventing protein aggregation, and thus participating in maintaining protein homeostasis in the cell. During their functional cycle, they bind unfolded client proteins inside their double ring structure and promote protein folding by closing the ring chamber in an adenosine 5'-triphosphate (ATP)-dependent manner. Although the static structures of fully open and closed forms of chaperonins were solved by x-ray crystallography or electron microscopy, elucidating the mechanisms of such ATP-driven molecular events requires studying the proteins at the structural level under working conditions. We introduce an approach that combines site-specific nuclear magnetic resonance observation of very large proteins, enabled by advanced isotope labeling methods, with an in situ ATP regeneration system. Using this method, we provide functional insight into the 1-MDa large hsp60 chaperonin while processing client proteins and reveal how nucleotide binding, hydrolysis, and release control switching between closed and open states. While the open conformation stabilizes the unfolded state of client proteins, the internalization of the client protein inside the chaperonin cavity speeds up its functional cycle. This approach opens new perspectives to study structures and mechanisms of various ATP-driven biological machineries in the heat of action.
Fichier principal
Vignette du fichier
Mas et al. Chaperonin 2018.pdf (2.97 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-01912129 , version 1 (22-06-2021)

Identifiants

Citer

Guillaume Mas, Jia-Ying Guan, Elodie Crublet, Elisa Colas Debled, Christine Moriscot, et al.. Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle. Science Advances , 2018, 4 (9), pp.eaau4196. ⟨10.1126/sciadv.aau4196⟩. ⟨hal-01912129⟩
56 Consultations
29 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More