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dc.contributor.authorVos, M.R.
dc.contributor.authorPiraino, B.
dc.contributor.authorLaBreck, C.J.
dc.contributor.authorRahmani, N.
dc.contributor.authorTrebino, C.E.
dc.contributor.authorSchoenle, M.
dc.contributor.authorPeti, W.
dc.contributor.authorCamberg, J.L.
dc.contributor.authorPage, R.
dc.date.accessioned2022-03-17T01:56:57Z
dc.date.available2022-03-17T01:56:57Z
dc.date.issued2022
dc.identifier.citationVos, M. R., Piraino, B., LaBreck, C. J., Rahmani, N., Trebino, C. E., Schoenle, M., Peti, W., Camberg, J. L., & Page, R. (2022). Degradation of the E. coli antitoxin MqsA by the proteolytic complex ClpXP is regulated by zinc occupancy and oxidation. Journal of Biological Chemistry.
dc.identifier.issn0021-9258
dc.identifier.pmid34974059
dc.identifier.doi10.1016/j.jbc.2021.101557
dc.identifier.urihttp://hdl.handle.net/10150/663576
dc.description.abstractIt is well established that the antitoxins of toxin-antitoxin (TA) systems are selectively degraded by bacterial proteases in response to stress. However, how distinct stressors result in the selective degradation of specific antitoxins remain unanswered. MqsRA is a TA system activated by various stresses, including oxidation. Here, we reconstituted the Escherichia coli ClpXP proteolytic machinery in vitro to monitor degradation of MqsRA TA components. We show that the MqsA antitoxin is a ClpXP proteolysis substrate, and that its degradation is regulated by both zinc occupancy in MqsA and MqsR toxin binding. Using NMR chemical shift perturbation mapping, we show that MqsA is targeted directly to ClpXP via the ClpX substrate targeting N-domain, and ClpX mutations that disrupt N-domain binding inhibit ClpXP-mediated degradation in vitro. Finally, we discovered that MqsA contains a cryptic N-domain recognition sequence that is accessible only in the absence of zinc and MqsR toxin, both of which stabilize the MqsA fold. This recognition sequence is transplantable and sufficient to target a fusion protein for degradation in vitro and in vivo. Based on these results, we propose a model in which stress selectively targets nascent and zinc-free MqsA, resulting in exposure of the ClpX recognition motif for ClpXP-mediated degradation. © 2022 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.language.isoen
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.
dc.rightsCopyright © 2022 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleDegradation of the E. coli antitoxin MqsA by the proteolytic complex ClpXP is regulated by zinc occupancy and oxidation
dc.typeArticle
dc.typetext
dc.contributor.departmentDepartment of Chemistry and Biochemistry, University of Arizona
dc.identifier.journalJournal of Biological Chemistry
dc.description.noteOpen access journal
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
dc.eprint.versionFinal published version
dc.source.journaltitleJournal of Biological Chemistry
refterms.dateFOA2022-03-17T01:56:57Z


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Copyright © 2022 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright © 2022 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).