6l2a

From Proteopedia

(Difference between revisions)

Current revision

A mutant form of M. tb toxin MazEF-mt1

Structural highlights

6l2a is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9004467Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MAZF9_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 MazE9. Acts as an mRNA interferase, specifically cleaving between U and C in UAC sequences. May cleave its cognate antitoxin's gene (PubMed:25608501). In E.coli expression with non-cognate antitoxins VapB27 and VapB40 partially neutralizes the toxin.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Toxin-antitoxin (TA) systems, which regulate many important cellular processes, are abundantly present in prokaryotic organisms. MazEF is a common type of TA system implicated in the formation of "persisters cells" of the pathogen Mycobacterium tuberculosis, which contains 10 such systems. However, the exact function and inhibition mode of each MazF protein are not quite understood. Here, we report four high-resolution crystal structures of MazF-mt1 in various forms, including one in complex with MazE-mt1. The toxin displayed two unique interlocked loops that allow the formation of a tight dimer. These loops would open upon interacting with the MazE-mt1 antitoxin mediated by the last two helices of MazE-mt1. With our structure-based design, a mutant that could bind to the antitoxin with an enhanced affinity was produced. Combined crystallographic and biochemical studies further revealed that the binding affinity of MazE-mt1 to MazF-mt1 was mainly attributed to its alpha3 helical region, while the terminal helix eta1 contributes very little or even negatively to the association of the pair, in stark contrast to the MazEF-mt9 system. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE/F-mt1 TA pair, which may reflect the functional differences between different TA systems.

Conserved Conformational Changes in the Regulation of Mycobacterium tuberculosis MazEF-mt1.,Chen R, Zhou J, Sun R, Du C, Xie W ACS Infect Dis. 2020 Jul 10;6(7):1783-1795. doi: 10.1021/acsinfecdis.0c00048., Epub 2020 Jun 16. PMID:32485099^[6]

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

References

↑ Zhu L, Zhang Y, Teh JS, Zhang J, Connell N, Rubin H, Inouye M. Characterization of mRNA interferases from Mycobacterium tuberculosis. J Biol Chem. 2006 Jul 7;281(27):18638-43. Epub 2006 Apr 12. PMID:16611633 doi:http://dx.doi.org/10.1074/jbc.M512693200
↑ Gupta A. Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2009 Jan;290(1):45-53. doi:, 10.1111/j.1574-6968.2008.01400.x. Epub 2008 Nov 10. PMID:19016878 doi:http://dx.doi.org/10.1111/j.1574-6968.2008.01400.x
↑ Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec;5(12):e1000767. doi: 10.1371/journal.pgen.1000767. Epub 2009, Dec 11. PMID:20011113 doi:http://dx.doi.org/10.1371/journal.pgen.1000767
↑ Zhu L, Sharp JD, Kobayashi H, Woychik NA, Inouye M. Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and functionally interact. J Biol Chem. 2010 Dec 17;285(51):39732-8. doi: 10.1074/jbc.M110.163105. Epub 2010, Sep 27. PMID:20876537 doi:http://dx.doi.org/10.1074/jbc.M110.163105
↑ Tiwari P, Arora G, Singh M, Kidwai S, Narayan OP, Singh R. MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs. Nat Commun. 2015 Jan 22;6:6059. doi: 10.1038/ncomms7059. PMID:25608501 doi:http://dx.doi.org/10.1038/ncomms7059
↑ Chen R, Zhou J, Sun R, Du C, Xie W. Conserved Conformational Changes in the Regulation of Mycobacterium tuberculosis MazEF-mt1. ACS Infect Dis. 2020 Jul 10;6(7):1783-1795. doi: 10.1021/acsinfecdis.0c00048., Epub 2020 Jun 16. PMID:32485099 doi:http://dx.doi.org/10.1021/acsinfecdis.0c00048

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6l2a"

Categories: Large Structures | Mycobacterium tuberculosis | Chen R | Xie W | Zhou J

@@ Line 3: / Line 3: @@
 <StructureSection load='6l2a' size='340' side='right'caption='[[6l2a]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6l2a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L2A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6l2a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L2A FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mazF9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9004467&#8491;</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6l2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l2a OCA], [https://pdbe.org/6l2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l2a RCSB], [https://www.ebi.ac.uk/pdbsum/6l2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l2a ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/A0A0E7Y7J2_MYCTX A0A0E7Y7J2_MYCTX]] Toxic component of a type II toxin-antitoxin (TA) system.[PIRNR:PIRNR033490]
+[https://www.uniprot.org/uniprot/MAZF9_MYCTU MAZF9_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 MazE9. Acts as an mRNA interferase, specifically cleaving between U and C in UAC sequences. May cleave its cognate antitoxin's gene (PubMed:25608501). In E.coli expression with non-cognate antitoxins VapB27 and VapB40 partially neutralizes the toxin.<ref>PMID:16611633</ref> <ref>PMID:19016878</ref> <ref>PMID:20011113</ref> <ref>PMID:20876537</ref> <ref>PMID:25608501</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Chen, R]]
+[[Category: Mycobacterium tuberculosis]]
-[[Category: Xie, W]]
+[[Category: Chen R]]
-[[Category: Zhou, J]]
+[[Category: Xie W]]
-[[Category: Protein engineering]]
+[[Category: Zhou J]]
-[[Category: Rna endonlease]]
-[[Category: Toxin]]

6l2a

From Proteopedia

Current revision

A mutant form of M. tb toxin MazEF-mt1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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