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Nat Chem Biol. 2015 Mar;11(3):201-6. doi: 10.1038/nchembio.1732. Epub 2015 Jan 19.

Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine.

Author information

1
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
2
1] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Abstract

Hexameric ATP-dependent proteases and protein remodeling machines use conserved loops that line the axial pore to apply force to substrates during the mechanical processes of protein unfolding and translocation. Whether loops from multiple subunits act independently or coordinately in these processes is a critical aspect of the mechanism but is currently unknown for any AAA+ machine. By studying covalently linked hexamers of the Escherichia coli ClpX unfoldase bearing different numbers and configurations of wild-type and mutant pore loops, we show that loops function synergistically, and the number of wild-type loops required for efficient degradation is dependent on the stability of the protein substrate. Our results support a mechanism in which a power stroke initiated in one subunit of the ClpX hexamer results in the concurrent movement of all six pore loops, which coordinately grip and apply force to the substrate.

PMID:
25599533
PMCID:
PMC4333055
DOI:
10.1038/nchembio.1732
[Indexed for MEDLINE]
Free PMC Article

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