Unavoidable Disasters: the Hsp70 Chaperone Can Only Prevent Aggregation Over a Limited Time Span

Hsp70 in the Escherichia coli chaperone system prevents aggregation only for weakly aggregation-prone clients over timescales up to ~79 years, but not for strongly aggregation-prone clients.

• Why it matters: The field lacks quantitative, client-specific predictions linking chaperone action to kinetic and thermodynamic properties that determine when aggregation begins.
• What they did: The CHAMPION70 computational model simulates folding and aggregation using experimentally determined folding/unfolding/aggregation rate constants for the Escherichia coli Hsp70 system.
• The result: For strongly aggregation-prone clients, aggregation is predicted to begin within a few minutes even at higher-than-physiological Hsp70 concentrations, implying Hsp70 delays but does not eliminate aggregation.

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