ToxT
From Proteopedia
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| - | <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Barrel/1'>A nine-stranded beta sheet sandwich</scene> or "jelly-roll" with three other alpha helices (overall making up the <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/N-terminus/1'>N-terminus</scene>) constitutes a <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Binding_pocket/1'>binding pocket</scene that contains a ligand: <i>cis</i>-palmitoleate,<!--insert scene here!--> <ref name="structure">PMID: 20133655</ref> which appears to have a negative effect on virulence when present in vitro. This unsaturated fatty acid, like other UFAs,[http://en.wikipedia.org/wiki/Fatty_acid#Unsaturated_fatty_acids] tend to inhibit genes under the control of ToxT. The | + | <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Barrel/1'>A nine-stranded beta sheet sandwich</scene> or "jelly-roll" with three other alpha helices (overall making up the <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/N-terminus/1'>N-terminus</scene>) constitutes a <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Binding_pocket/1'>binding pocket</scene> that contains a ligand: <i>cis</i>-palmitoleate,<!--insert scene here!--> <ref name="structure">PMID: 20133655</ref> which appears to have a negative effect on virulence when present in vitro. This unsaturated fatty acid, like other UFAs,[http://en.wikipedia.org/wiki/Fatty_acid#Unsaturated_fatty_acids] tend to inhibit genes under the control of ToxT. The |
Specifically, the <i>cis</i>-palmitoleate appears to bind directly to ToxT, change its conformation, and thus lower the ability to bind DNA and form dimers.<ref name="structure">PMID: 20133655</ref> | Specifically, the <i>cis</i>-palmitoleate appears to bind directly to ToxT, change its conformation, and thus lower the ability to bind DNA and form dimers.<ref name="structure">PMID: 20133655</ref> | ||
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Revision as of 16:18, 29 November 2011
The crystal structure of ToxT is resolved in monomeric form, after isolation from Vibrio cholerae strain O395.[1]
Contents |
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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Ligand
In this resolved structure, [5] is present and bound in the beta sheet barrel (further discussed below). This unsaturated fatty acid reduces virulence expression in Vibrio cholerae.
Other Structural Features
ToxT belongs to a family of transcriptional regulators headed by and known as AraC.[1] The AraC family is characterized by a 100 amino acid region of sequence similarity that forms a with two helix-turn-helix motifs (helix in blue, turn in teal). [2] The two HTH regions are linked by a very polar alpha helix (shown in black). The overall domain is composed of seven alpha helices, and is located at the C-terminus.[1]
or "jelly-roll" with three other alpha helices (overall making up the ) constitutes a that contains a ligand: cis-palmitoleate, [1] which appears to have a negative effect on virulence when present in vitro. This unsaturated fatty acid, like other UFAs,[6] tend to inhibit genes under the control of ToxT. The
Specifically, the cis-palmitoleate appears to bind directly to ToxT, change its conformation, and thus lower the ability to bind DNA and form dimers.[1]
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 ctx promoter to generate cholera toxin appears to be possible only in the dimer form.[3]ToxT binds to thirteen base pair sequences (can be single, direct, or inverted repeats) called toxboxes in order to activate their respective promoters.[7]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 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
- ↑ 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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