Physics-Biology interface seminar: Alessandro Barducci


11:00 - 12:00

LPTMS, salle 201, 2ème étage, Bât 100, Campus d'Orsay
15 Rue Georges Clemenceau, Orsay, 91405

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Molecular chaperones as cellular non-equilibrium machines.

Alessandro Barducci (Centre de Biochimie Structurale-INSERM, Montpellier)

Molecular chaperones are a vast class of proteins that maintain protein homeostasis in the cell and are thus essential for cell viability. In order to assist protein folding and prevent misfolding, most chaperones proceed through conformational cycles that are regulated by complex interaction networks and fueled by ATP-hydrolysis. A remarkable example are the 70-kDalton heat shock proteins (Hsp70s), which are essential in prokaryotes and eukaryotes and are involved in co-translational folding, refolding of misfolded and aggregated proteins, protein translocation, and protein degradation. While the investigation of Hsp70 cycle has attracted great attention in the last decades, the actual role of ATP-hydrolysis and, thus of energy consumption, in the chaperone function has been long unaddressed. Here we will prove how biochemical data, recent single-molecule fluorescence experiments and molecular simulations can be combined into an appropriate theoretical framework to show that: i) ATP hydrolysis allows Hsp70 chaperones to increase their affinity for the client proteins beyond the bounds imposed by equilibrium thermodynamics ii) This ultra-affinity can be exploited to perform mechanical work on client proteins thus avoiding the formation of misfolded and potentially cytotoxic species.

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