دورية أكاديمية
DNA binding reveals hidden interdomain allostery of a MazE antitoxin from Mycobacterium tuberculosis.
| العنوان: | DNA binding reveals hidden interdomain allostery of a MazE antitoxin from Mycobacterium tuberculosis. |
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| المؤلفون: | Eun HJ; The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea., Lee SY; Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon-si, 11160, Gyeonggi-Do, Republic of Korea., Lee KY; Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon-si, 11160, Gyeonggi-Do, Republic of Korea. Electronic address: kiyoung198395@gmail.com. |
| المصدر: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 May 28; Vol. 710, pp. 149898. Date of Electronic Publication: 2024 Apr 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002- >: San Diego, CA : Elsevier Original Publication: New York, Academic Press. |
| مواضيع طبية MeSH: | Mycobacterium tuberculosis*/metabolism , Antitoxins*/chemistry, Models, Molecular ; Transcription Factors/metabolism ; DNA/metabolism ; Bacterial Proteins/metabolism |
| مستخلص: | Type II toxin-antitoxin (TA) systems are ubiquitously distributed genetic elements in prokaryotes and are crucial for cell maintenance and survival under environmental stresses. The antitoxin is a modular protein consisting of the disordered C-terminal region that physically contacts and neutralizes the cognate toxin and the well-folded N-terminal DNA binding domain responsible for autorepression of TA transcription. However, how the two functional domains communicate is largely unknown. Herein, we determined the crystal structure of the N-terminal domain of the type II antitoxin MazE-mt10 from Mycobacterium tuberculosis, revealing a homodimer of the ribbon-helix-helix (RHH) fold with distinct DNA binding specificity. NMR studies demonstrated that full-length MazE-mt10 forms the helical and coiled states in equilibrium within the C-terminal region, and that helical propensity is allosterically enhanced by the N-terminal binding to the cognate operator DNA. This coil-to-helix transition may promote toxin binding/neutralization of MazE-mt10 and further stabilize the TA-DNA transcription repressor. This is supported by many crystal structures of type II TA complexes in which antitoxins form an α-helical structure at the TA interface. The hidden helical state of free MazE-mt10 in solution, favored by DNA binding, adds a new dimension to the regulatory mechanism of type II TA systems. Furthermore, complementary approaches using X-ray crystallography and NMR allow us to study the allosteric interdomain interplay of many other full-length antitoxins of type II TA systems. Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Coil-to-helix transition; DNA binding; MazE antitoxin; NMR; Toxin neutralization site; X-ray crystallography |
| المشرفين على المادة: | 0 (Antitoxins) 0 (Transcription Factors) 9007-49-2 (DNA) 0 (Bacterial Proteins) |
| تواريخ الأحداث: | Date Created: 20240410 Date Completed: 20240422 Latest Revision: 20240422 |
| رمز التحديث: | 20240422 |
| DOI: | 10.1016/j.bbrc.2024.149898 |
| PMID: | 38598903 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2104 |
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| DOI: | 10.1016/j.bbrc.2024.149898 |