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==2.09 Angstrom resolution crystal structure of tetrameric HigBA toxin-antitoxin complex from E.coli==
<StructureSection load='6kml' size='340' side='right'caption='[[6kml]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kml]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KML FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.095&#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=6kml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kml OCA], [https://pdbe.org/6kml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kml RCSB], [https://www.ebi.ac.uk/pdbsum/6kml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kml ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HIGB_ECOLI HIGB_ECOLI] Toxic component of a toxin-antitoxin (TA) module. A probable translation-dependent mRNA interferase. Overexpression causes cessation of cell growth and inhibits cell proliferation via inhibition of translation; this blockage is overcome by subsequent expression of antitoxin HigA. Overexpression causes cleavage of a number of mRNAs in a translation-dependent fashion, suggesting this is an mRNA interferase.<ref>PMID:19943910</ref> 
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== Publication Abstract from PubMed ==
The toxin-antitoxin (TA) systems are small operon systems that are involved in important physiological processes in bacteria such as stress response and persister cell formation. Escherichia coli HigBA complex belongs to the type II TA systems and consists of a protein toxin called HigB and a protein antitoxin called HigA. The toxin HigB is a ribosome-dependent endoribonuclease that cleaves the translating mRNAs at the ribosome A site. The antitoxin HigA directly binds the toxin HigB, rendering the HigBA complex catalytically inactive. The existing biochemical and structural studies had revealed that the HigBA complex forms a heterotetrameric assembly via dimerization of HigA antitoxin. Here, we report a high-resolution crystal structure of E. coli HigBA complex that revealed a well-ordered DNA binding domain in HigA antitoxin. Using SEC-MALS and ITC methods, we have determined the stoichiometry of complex formation between HigBA and a 33 bp DNA and report that HigBA complex as well as HigA homodimer bind to the palindromic DNA sequence with nano molar affinity. Using E. coli growth assays, we have probed the roles of key, putative active site residues in HigB. Spectroscopic methods (CD and NMR) and molecular dynamics simulations study revealed intrinsic dynamic in antitoxin in HigBA complex, which may explain the large conformational changes in HigA homodimer in free and HigBA complexes observed previously. We also report a truncated, heterodimeric form of HigBA complex that revealed possible cleavage sites in HigBA complex, which can have implications for its cellular functions.

2.09 A Resolution structure of E. coli HigBA toxin-antitoxin complex reveals an ordered DNA-binding domain and intrinsic dynamics in antitoxin.,Jadhav PV, Sinha VK, Chugh S, Kotyada C, Bachhav D, Singh R, Rothweiler U, Singh M Biochem J. 2020 Oct 30;477(20):4001-4019. doi: 10.1042/BCJ20200363. PMID:33000860<ref>PMID:33000860</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6kml" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Jadhav P]]
[[Category: Rothweiler U]]
[[Category: Singh M]]
[[Category: Sinha VK]]