Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine
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Baker_Dynamic and static.pdf
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Author(s)
Glynn, Steven E.
Nager, Andrew Ross
Baker, Tania
Sauer, Robert T
Date Issued
May 2012
Journal
Nature Structural & Molecular Biology
Publisher
Nature Publishing Group
Citation
Glynn, Steven E, Andrew R Nager, Tania A Baker, and Robert T Sauer. “Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine.” Nature Structural & Molecular Biology 19, no. 6 (May 6, 2012): 616-622.
Version
Author's final manuscript
Abstract
In the Escherichia coli ClpXP protease, a hexameric ClpX ring couples ATP binding and hydrolysis to mechanical protein unfolding and translocation into the ClpP degradation chamber. Rigid-body packing between the small AAA+ domain of each ClpX subunit and the large AAA+ domain of its neighbor stabilizes the hexamer. By connecting the parts of each rigid-body unit with disulfide bonds or linkers, we created covalently closed rings that retained robust activity. A single-residue insertion in the hinge that connects the large and small AAA+ domains and forms part of the nucleotide-binding site uncoupled ATP hydrolysis from productive unfolding. We propose that ATP hydrolysis drives changes in the conformation of one hinge and its flanking domains and that the changes are propagated around the AAA+ ring through the topologically constrained set of rigid-body units and hinges to produce coupled ring motions that power substrate unfolding.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/nsmb.2288
