View source for 3hpw


==CcdB dimer in complex with one C-terminal CcdA domain==
<StructureSection load='3hpw' size='340' side='right'caption='[[3hpw]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3hpw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [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=3HPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HPW 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]] 1.452&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3hpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hpw OCA], [https://pdbe.org/3hpw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hpw RCSB], [https://www.ebi.ac.uk/pdbsum/3hpw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hpw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CCDB_ECOLI CCDB_ECOLI] Toxic component of a toxin-antitoxin (TA) module, functioning in plasmid maintainence. Responsible for the post-segregational killing (PSK) of plasmid-free cells, also referred to as a plasmid addiction system. Half-life of over 2 hours. Cell killing by CcdB is accompanied by filamentation, defects in chromosome and plasmid segregation, defects in cell division, formation of anucleate cells, decreased DNA synthesis and plasmid loss. Interferes with the activity of DNA gyrase, inducing it to form a covalent GyrA-DNA complex that cannot be resolved, thus promoting breakage of plasmid and chromosomal DNA. DNA breakage requires hydrolyzable ATP. Toxicity is inhibited by labile antitoxin CcdA, which blocks the activity of CcdB; CcdA also removes bound CcdB protein from the CcdB-GyrA complex by forming a CcdA-CcdB complex, a process termed rejuvenation. Also acts to inhibit partitioning of the chromosomal DNA. Functions as a transcriptional corepressor for the ccdAB operon, repression also requires CcdA.<ref>PMID:6327993</ref> <ref>PMID:2651399</ref> <ref>PMID:6308648</ref> <ref>PMID:2615761</ref> <ref>PMID:1324324</ref> <ref>PMID:8604132</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hp/3hpw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hpw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Toxin-antitoxin modules are small regulatory circuits that ensure survival of bacterial populations under challenging environmental conditions. The ccd toxin-antitoxin module on the F plasmid codes for the toxin CcdB and its antitoxin CcdA. CcdB poisons gyrase while CcdA actively dissociates CcdB:gyrase complexes in a process called rejuvenation. The CcdA:CcdB ratio modulates autorepression of the ccd operon. The mechanisms behind both rejuvenation and regulation of expression are poorly understood. We show that CcdA binds consecutively to two partially overlapping sites on CcdB, which differ in affinity by six orders of magnitude. The first, picomolar affinity interaction triggers a conformational change in CcdB that initiates the dissociation of CcdB:gyrase complexes by an allosteric segmental binding mechanism. The second, micromolar affinity binding event regulates expression of the ccd operon. Both functions of CcdA, rejuvenation and autoregulation, are mechanistically intertwined and depend crucially on the intrinsically disordered nature of the CcdA C-terminal domain.

Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered protein domain.,De Jonge N, Garcia-Pino A, Buts L, Haesaerts S, Charlier D, Zangger K, Wyns L, De Greve H, Loris R Mol Cell. 2009 Jul 31;35(2):154-63. PMID:19647513<ref>PMID:19647513</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3hpw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Buts L]]
[[Category: De Jonge N]]
[[Category: Garcia-Pino A]]
[[Category: Loris R]]