8YPJ
Cyrstal structure of the MazE-mt10 Antitoxin from Mycobacterium tuberculosis
Summary for 8YPJ
Entry DOI | 10.2210/pdb8ypj/pdb |
Descriptor | Antitoxin, PHOSPHATE ION (3 entities in total) |
Functional Keywords | antitoxin, maze, mycobacterium tuberculosis, dna binding, signaling protein |
Biological source | Mycobacterium tuberculosis |
Total number of polymer chains | 2 |
Total formula weight | 16377.37 |
Authors | |
Primary citation | Eun, H.J.,Lee, S.Y.,Lee, K.Y. DNA binding reveals hidden interdomain allostery of a MazE antitoxin from Mycobacterium tuberculosis. Biochem.Biophys.Res.Commun., 710:149898-149898, 2024 Cited by PubMed Abstract: 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. PubMed: 38598903DOI: 10.1016/j.bbrc.2024.149898 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.91 Å) |
Structure validation
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