Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2012 May 6;19(6):616-22. doi: 10.1038/nsmb.2288.

Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine.

Author information

  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

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.

PMID:
22562135
[PubMed - indexed for MEDLINE]
PMCID:
PMC3372766
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk