Allosteric regulation of DegS protease subunits through a shared energy landscape
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Sauer_Allosteric regulation.pdf
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2.01 MB
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Author(s)
Mauldin, Randall V.
Sauer, Robert T
Date Issued
December 2012
Journal
Nature Chemical Biology
Publisher
Nature Publishing Group
Citation
Mauldin, Randall V., and Robert T Sauer. “Allosteric regulation of DegS protease subunits through a shared energy landscape.” Nature Chemical Biology 9, no. 2 (December 2, 2012): 90-96.
Version
Author's final manuscript
Abstract
The PDZ domains of the trimeric DegS protease bind unassembled outer-membrane proteins (OMPs) that accumulate in the Escherichia coli periplasm. This cooperative binding reaction triggers a proteolytic cascade that activates a transcriptional stress response. To dissect the mechanism of allosteric activation, we generated hybrid DegS trimers with different numbers of PDZ domains and/or protease-domain mutations. By studying the chemical reactivity and enzymatic properties of these hybrids, we show that all subunits experience a strongly coupled energetic landscape. For example, OMP peptide binding to a single PDZ domain stimulates active site chemical modification and proteolytic cleavage in the attached and neighboring protease domains. OMP peptide binding relieves inhibitory PDZ interactions, whereas the interfaces between protease domains in the trimeric DegS core mediate positively cooperative activation driven by both substrate binding and inhibition relief.
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.1135
