Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine
Name
Sauer_Coordinated gripping.pdf
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Author(s)
Iosefson, Ohad
Nager, Andrew Ross
Baker, Tania
Sauer, Robert T.
Date Issued
January 2015
Journal
Nature Chemical Biology
Publisher
Nature Publishing Group
Citation
Iosefson, Ohad et al. “Coordinated Gripping of Substrate by Subunits of a AAA+ Proteolytic Machine.” Nature Chemical Biology 11.3 (2015): 201–206.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nchembio.1732
