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4me7

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Crystal structure of Bacillus subtilis toxin MazF in complex with cognate antitoxin MazE

Structural highlights

4me7 is a 6 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.918Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENDOA_BACSU Toxic component of a toxin-antitoxin (TA) module. Has specificity for UACAU sequences, claving after the first U and yielding cleavage products with 3' phosphate and 5' hydroxyl groups. Overexpression is toxic for cell growth, probably by inhibiting protein synthesis through the cleavage of single-stranded RNA. The toxicity is reversed by the antitoxin EndoAI. Toxin activity cannot be inhibited by MazE from E.coli.^[1] ^[2]

Publication Abstract from PubMed

MazF is an mRNA interferase, which, upon activation during stress conditions, cleaves mRNAs in a sequence-specific manner, resulting in cellular growth arrest. During normal growth conditions, the MazF toxin is inactivated through binding to its cognate antitoxin, MazE. How MazF specifically recognizes its mRNA target and carries out cleavage and how the formation of the MazE-MazF complex inactivates MazF remain unclear. We present crystal structures of MazF in complex with mRNA substrate and antitoxin MazE in Bacillus subtilis. The structure of MazF in complex with uncleavable UUdUACAUAA RNA substrate defines the molecular basis underlying the sequence-specific recognition of UACAU and the role of residues involved in the cleavage through site-specific mutational studies. The structure of the heterohexameric (MazF)2-(MazE)2-(MazF)2 complex in Bacillus subtilis, supplemented by mutational data, demonstrates that the positioning of the C-terminal helical segment of MazE within the RNA-binding channel of the MazF dimer prevents mRNA binding and cleavage by MazF.

Structural Basis of mRNA Recognition and Cleavage by Toxin MazF and Its Regulation by Antitoxin MazE in Bacillus subtilis.,Simanshu DK, Yamaguchi Y, Park JH, Inouye M, Patel DJ Mol Cell. 2013 Oct 8. pii: S1097-2765(13)00676-X. doi:, 10.1016/j.molcel.2013.09.006. PMID:24120662^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pellegrini O, Mathy N, Gogos A, Shapiro L, Condon C. The Bacillus subtilis ydcDE operon encodes an endoribonuclease of the MazF/PemK family and its inhibitor. Mol Microbiol. 2005 Jun;56(5):1139-48. PMID:15882409 doi:MMI4606
↑ Park JH, Yamaguchi Y, Inouye M. Bacillus subtilis MazF-bs (EndoA) is a UACAU-specific mRNA interferase. FEBS Lett. 2011 Aug 4;585(15):2526-32. doi: 10.1016/j.febslet.2011.07.008. Epub, 2011 Jul 13. PMID:21763692 doi:http://dx.doi.org/10.1016/j.febslet.2011.07.008
↑ Simanshu DK, Yamaguchi Y, Park JH, Inouye M, Patel DJ. Structural Basis of mRNA Recognition and Cleavage by Toxin MazF and Its Regulation by Antitoxin MazE in Bacillus subtilis. Mol Cell. 2013 Oct 8. pii: S1097-2765(13)00676-X. doi:, 10.1016/j.molcel.2013.09.006. PMID:24120662 doi:http://dx.doi.org/10.1016/j.molcel.2013.09.006