6a6x
From Proteopedia
The crystal structure of the Mtb MazE-MazF-mt9 complex
Structural highlights
Function[MAZF7_MYCTU] Toxic component of a type II toxin-antitoxin (TA) module. Upon expression in E.coli and M.smegmatis inhibits cell growth and colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin MazE7 (PubMed:19016878, PubMed:20011113). Probably an endoribonuclease (By similarity).[UniProtKB:P9WIH9][1] [2] [MAZE7_MYCTU] Antitoxin component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli but not in M.smegmatis neutralizes the effect of cognate toxin MazF7.[3] Publication Abstract from PubMedToxin-antitoxin (TA) modules widely exist in bacteria, and their activities are associated with the persister phenotype of the pathogen Mycobacterium tuberculosis ( M. tb). M. tb causes tuberculosis, a contagious and severe airborne disease. There are 10 MazEF TA systems in M. tb that play important roles in stress adaptation. How the antitoxins antagonize toxins in M. tb or how the 10 TA systems crosstalk to each other are of interest, but the detailed molecular mechanisms are largely unclear. MazEF-mt9 is a unique member among the MazEF family due to its tRNase activity, which is usually carried out by the VapC toxins. Here, we present the cocrystal structure of the MazEF-mt9 complex at 2.7 A. By characterizing the association mode between the TA pairs through various techniques, we found that MazF-mt9 bound not only its cognate antitoxin but also the noncognate antitoxin MazE-mt1, a phenomenon that could be also observed in vivo. Based on our structural and biochemical work, we propose that the cognate and heterologous interactions among different TA systems work together in vivo to relieve the toxicity of MazF-mt9 toward M. tb cells. Structural and Biochemical Characterization of the Cognate and Heterologous Interactions of the MazEF-mt9 TA System.,Chen R, Tu J, Tan Y, Cai X, Yang C, Deng X, Su B, Ma S, Liu X, Ma P, Du C, Xie W ACS Infect Dis. 2019 Jul 3. doi: 10.1021/acsinfecdis.9b00001. PMID:31267737[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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