ToxT
From Proteopedia
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<b>ToxT</b> is a molecule at the end of a transcriptional cascade that autoregulates the transcription of the primary virulence factors of <i>Vibrio cholerae</i>[http://en.wikipedia.org/wiki/Vibrio_cholerae] and itself. These two factors, cholera toxin (CT)[http://http://en.wikipedia.org/wiki/Cholera_toxin] and the toxin co-regulated pilus (TCP), are instrumental in causing the disease <b>cholera</b>[http://en.wikipedia.org/wiki/Cholera]. This is an intestinal infection resulting in massive water loss in the affected individual, causing extreme dehydration.[http://en.wikipedia.org/wiki/Cholera] | <b>ToxT</b> is a molecule at the end of a transcriptional cascade that autoregulates the transcription of the primary virulence factors of <i>Vibrio cholerae</i>[http://en.wikipedia.org/wiki/Vibrio_cholerae] and itself. These two factors, cholera toxin (CT)[http://http://en.wikipedia.org/wiki/Cholera_toxin] and the toxin co-regulated pilus (TCP), are instrumental in causing the disease <b>cholera</b>[http://en.wikipedia.org/wiki/Cholera]. This is an intestinal infection resulting in massive water loss in the affected individual, causing extreme dehydration.[http://en.wikipedia.org/wiki/Cholera] | ||
<StructureSection load='3gbg' color='cpk' size='500' frame='true' align='right' caption='ToxT, 1.9 Angstrom resolution crystal structure' > | <StructureSection load='3gbg' color='cpk' size='500' frame='true' align='right' caption='ToxT, 1.9 Angstrom resolution crystal structure' > | ||
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==Ligand== | ==Ligand== | ||
In this resolved structure, <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Pam/2'>cis-palmitoleate</scene>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=3gbg&template=ligands.html&l=1.1] is present and bound in the beta sheet barrel (further discussed below). This unsaturated fatty acid reduces virulence expression in <i>Vibrio cholerae</i>. | In this resolved structure, <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Pam/2'>cis-palmitoleate</scene>[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=3gbg&template=ligands.html&l=1.1] is present and bound in the beta sheet barrel (further discussed below). This unsaturated fatty acid reduces virulence expression in <i>Vibrio cholerae</i>. | ||
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| - | Though the structure shown is a monomer with two overall domains (N-terminal and C-terminal), ToxT tends to form a dimer. The preferred state of ToxT varies between promoters, but binding to the <i>ctx</i> promoter to generate cholera toxin appears to be possible only in the dimer form.<ref name="virstatin">PMID:17283330</ref>ToxT binds to thirteen base pair sequences (can be single, direct, or inverted repeats) called toxboxes in order to activate their respective promoters.[http://www.sigwiki.info/wiki/Signature:ToxBox] | + | Though the structure shown is a monomer with two overall domains (N-terminal and C-terminal), ToxT tends to form a dimer.<ref name="dimerization">PMID: 21415495 |
| + | </ref> The preferred state of ToxT varies between promoters, but binding to the <i>ctx</i> promoter to generate cholera toxin appears to be possible only in the dimer form.<ref name="virstatin">PMID:17283330</ref>ToxT binds to thirteen base pair sequences (can be single, direct, or inverted repeats) called toxboxes in order to activate their respective promoters.[http://www.sigwiki.info/wiki/Signature:ToxBox] | ||
</StructureSection> | </StructureSection> | ||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 17:01, 29 November 2011
The crystal structure of ToxT is resolved in monomeric form, after isolation from Vibrio cholerae strain O395.[1]
Introduction
ToxT is a molecule at the end of a transcriptional cascade that autoregulates the transcription of the primary virulence factors of Vibrio cholerae[1] and itself. These two factors, cholera toxin (CT)[2] and the toxin co-regulated pilus (TCP), are instrumental in causing the disease cholera[3]. This is an intestinal infection resulting in massive water loss in the affected individual, causing extreme dehydration.[4]
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Lowden MJ, Skorupski K, Pellegrini M, Chiorazzo MG, Taylor RK, Kull FJ. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2860-5. Epub 2010 Feb 1. PMID:20133655
- ↑ Martin RG, Rosner JL. The AraC transcriptional activators. Curr Opin Microbiol. 2001 Apr;4(2):132-7. PMID:11282467
- ↑ Weber GG, Klose KE. The complexity of ToxT-dependent transcription in Vibrio cholerae. Indian J Med Res. 2011 Feb;133(2):201-6. PMID:21415495
- ↑ Shakhnovich EA, Hung DT, Pierson E, Lee K, Mekalanos JJ. Virstatin inhibits dimerization of the transcriptional activator ToxT. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2372-7. Epub 2007 Feb 5. PMID:17283330 doi:10.1073/pnas.0611643104
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