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Title: Does the GroEL chaperonin actively speed folding or only isolate?
Plain: The bacterial machine GroEL encloses a misfolded protein in a cage, burns ATP and releases it, and many proteins fold only with its help. Whether it merely shields the protein from clumping or actively unfolds trapped states so that they can refold is disputed.
Precise: In the passive-cage model, a substrate folds inside the GroEL-GroES chamber (residence approximately 10 s per ATP cycle, approximate) at the same rate as at infinite dilution; in the iterative-annealing model, ATP-driven forces partially unfold misfolded states each cycle, raising the folded yield per cycle; confinement may also change the rate. For obligate substrates, measure the folding rate and yield per cycle inside the cage versus spontaneous folding at equal conditions, and identify which model predicts them.
Settled by: Single-molecule measurements of substrate conformation across successive GroEL cycles, compared with the per-cycle yield predicted by each model.
Kind: well-posed
Answer type: mechanism
References: (empty)
Literature status: contested
Status note: Thirumalai, Lorimer and Hyeon (Protein Science 2020, doi 10.1002/pro.3795) argue for iterative annealing; passive-cage and confinement-acceleration views remain in the literature.
Posed since: (empty)