Chaperonins are allosteric double-ring ATPases that mediate cellular protein folding. ATP binding and hydrolysis control opening and closing of the central chaperonin chamber, which transiently provides a protected environment for protein folding. During evolution, two strategies to close the chaperonin chamber have emerged. Archaeal and eukaryotic group II chaperonins contain a built-in lid, whereas bacterial chaperonins use a ring-shaped cofactor as a detachable lid. Here we show that the built-in lid is an allosteric regulator of group II chaperonins, which helps synchronize the subunits within one ring and, to our surprise, also influences inter-ring communication. The lid is dispensable for substrate binding and ATP hydrolysis, but is required for productive substrate folding. These regulatory functions of the lid may serve to allow the symmetrical chaperonins to function as 'two-stroke' motors and may also provide a timer for substrate encapsulation within the closed chamber.
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We thank M. Thanbichler, R. Andino and members of the Frydman laboratory for discussions and comments on the manuscript. S.R. thanks A. Böck for advice and discussions. J. Leigh (University of Washington) kindly provided M. maripaludis DNA. This research was supported by the US National Institutes of Health, the US National Institutes of Health Roadmap Initiative on Nanomedicine, the Studienstiftung des Deutschen Volkes and the Robert Welch Foundation.
The authors declare no competing financial interests.
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Reissmann, S., Parnot, C., Booth, C. et al. Essential function of the built-in lid in the allosteric regulation of eukaryotic and archaeal chaperonins. Nat Struct Mol Biol 14, 432–440 (2007). https://doi.org/10.1038/nsmb1236
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