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

Mas G, Guan J-Y, Crublet E, Debled EC, Moriscot C, Gans P, Schoehn G, Macek P, Schanda P, Boisbouvier J. 2018. Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle. Science Advances. 4(9), eaau4196.

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Journal Article | Published | English
Author
Mas, Guillaume; Guan, Jia-Ying; Crublet, Elodie; Debled, Elisa Colas; Moriscot, Christine; Gans, Pierre; Schoehn, Guy; Macek, Pavel; Schanda, PaulIST Austria ; Boisbouvier, Jerome
Abstract
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.
Publishing Year
Date Published
2018-09-19
Journal Title
Science Advances
Volume
4
Issue
9
Article Number
eaau4196
ISSN
IST-REx-ID

Cite this

Mas G, Guan J-Y, Crublet E, et al. Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle. Science Advances. 2018;4(9). doi:10.1126/sciadv.aau4196
Mas, G., Guan, J.-Y., Crublet, E., Debled, E. C., Moriscot, C., Gans, P., … Boisbouvier, J. (2018). Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.aau4196
Mas, Guillaume, Jia-Ying Guan, Elodie Crublet, Elisa Colas Debled, Christine Moriscot, Pierre Gans, Guy Schoehn, Pavel Macek, Paul Schanda, and Jerome Boisbouvier. “Structural Investigation of a Chaperonin in Action Reveals How Nucleotide Binding Regulates the Functional Cycle.” Science Advances. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/sciadv.aau4196.
G. Mas et al., “Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle,” Science Advances, vol. 4, no. 9. American Association for the Advancement of Science, 2018.
Mas G, Guan J-Y, Crublet E, Debled EC, Moriscot C, Gans P, Schoehn G, Macek P, Schanda P, Boisbouvier J. 2018. Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle. Science Advances. 4(9), eaau4196.
Mas, Guillaume, et al. “Structural Investigation of a Chaperonin in Action Reveals How Nucleotide Binding Regulates the Functional Cycle.” Science Advances, vol. 4, no. 9, eaau4196, American Association for the Advancement of Science, 2018, doi:10.1126/sciadv.aau4196.

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