{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:30Z","timestamp":1760145810011,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271322","2022A1515011768","2021A1515010880"],"award-info":[{"award-number":["32271322","2022A1515011768","2021A1515010880"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of the Guangdong Province","award":["32271322","2022A1515011768","2021A1515010880"],"award-info":[{"award-number":["32271322","2022A1515011768","2021A1515010880"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis is a worldwide plague caused by the pathogen Mycobacterium tuberculosis (M. tb). Toxin\u2013antitoxin (TA) systems are genetic elements abundantly present in prokaryotic organisms and regulate important cellular processes. MazEF is a TA system implicated in the formation of \u201cpersisters cells\u201d of M. tb, which contain more than 10 such members. However, the exact function and inhibition mode of each MazF are not fully understood. Here we report crystal structures of MazF-mt3 in its apo form and in complex with the C-terminal half of MazE-mt3. Structural analysis suggested that two long but disordered \u03b21\u2013\u03b22 loops would interfere with the binding of the cognate MazE-mt3 antitoxin. Similar loops are also present in the MazF-mt1 and -mt9 but are sustainably shortened in other M. tb MazF members, and these TA pairs behave distinctly in terms of their binding modes and their RNase activities. Systematic crystallographic and biochemical studies further revealed that the biochemical activities of M. tb toxins were combined results between the interferences from the characteristic loops and the electrostatic interactions between the cognate TA pairs. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE\/F TA pairs, which facilitate the structure-based peptide designs.<\/jats:p>","DOI":"10.3390\/ijms25179630","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T06:44:29Z","timestamp":1725518669000},"page":"9630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long Dynamic \u03b21\u2013\u03b22 Loops in M. tb MazF Toxins Affect the Interaction Modes and Strengths of the Toxin\u2013Antitoxin Pairs"],"prefix":"10.3390","volume":"25","author":[{"given":"Ziyun","family":"Tang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China"},{"name":"Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1696-9396","authenticated-orcid":false,"given":"Pengcheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China"},{"name":"Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2410-2135","authenticated-orcid":false,"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China"},{"name":"Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"unstructured":"World Health Organization (2023). 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