{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:06:51Z","timestamp":1740146811939,"version":"3.37.3"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["STEP 0652963"],"award-info":[{"award-number":["STEP 0652963"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006231","name":"Brookhaven National Laboratory","doi-asserted-by":"publisher","award":["LDRD 10-052"],"award-info":[{"award-number":["LDRD 10-052"]}],"id":[{"id":"10.13039\/100006231","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["LSAMP"],"award-info":[{"award-number":["LSAMP"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Aminoglycoside antibiotics interfere with the selection of cognate tRNAs during translation, resulting in the synthesis of aberrant proteins that are the ultimate cause of cell death. However, the toxic potential of aberrant proteins and how they avoid degradation by the cell\u2019s protein quality control (QC) machinery are not understood. Here we report that levels of the heat shock (HS) transcription factor \u03c332 increased sharply following exposure of <jats:italic>Escherichia coli<\/jats:italic> to the aminoglycoside kanamycin (Kan), suggesting that at least some of the aberrant proteins synthesized in these cells were recognized as substrates by DnaK, a molecular chaperone that regulates the HS response, the major protein QC pathway in bacteria. To further investigate aberrant protein toxic potential and interaction with cell QC factors, we studied an acutely toxic 48-residue polypeptide (ARF48) that is encoded by an alternate reading frame in a plant cDNA. As occurred in cells exposed to Kan, \u03c332 levels were strongly elevated following ARF48 expression, suggesting that ARF48 was recognized as a substrate by DnaK. Paradoxically, an internal 10-residue region that was tightly bound by DnaK <jats:italic>in vitro<\/jats:italic> also was required for the ARF48 toxic effect. Despite the increased levels of \u03c332, levels of several HS proteins were unchanged following ARF48 expression, suggesting that the HS response had been aborted. Nucleoids were condensed and cell permeability increased rapidly following ARF48 expression, together suggesting that ARF48 disrupts DNA-membrane interactions that could be required for efficient gene expression. Our results are consistent with earlier studies showing that aberrant proteins induced by aminoglycoside antibiotics disrupt cell membrane integrity. Insights into the mechanism for this effect could be gained by further study of the ARF48 model system.<\/jats:p>","DOI":"10.1371\/journal.pone.0258794","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T17:37:14Z","timestamp":1651253834000},"page":"e0258794","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A polypeptide model for toxic aberrant proteins induced by aminoglycoside 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