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| ==Structural Features== | | ==Structural Features== |
| <u>Similarities to CD4 in complex with gp120</u>. ToxT belongs to a family of transcriptional regulators headed by and known as AraC.<ref name="structure">PMID: 20133655</ref> The AraC family is characterized by a 100 amino acid region of sequence similarity that forms a <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Two_hth_domains/1'>DNA-binding domain</scene> with two helix-turn-helix motifs (one on either side of the black linker). <ref name="arac">PMID: 11282467</ref> This DNA binding domain is composed of seven alpha helices. HTH1 is composed of alpha helices five and six, while HTH2 is composed of alpha helices eight and nine. The two HTH regions are linked by the very polar alpha helix seven(shown in black). The overall domain is located at the C-terminus.<ref name="structure">PMID: 20133655</ref> Assuming ToxT is similar in mechanism to other AraC proteins, helix six from HTH1 and helix nine from HTH2 become aligned with the help of helix seven. Helix seven is positioned to attach to the N terminal binding pocket(the polar linking region) to allow binding to major consecutive grooves of target DNA (specific promoters for virulence genes).<ref name="structure">PMID: 20133655</ref>[http://www.pnas.org/content/107/7/2860/F3.large.jpg]. The conformation of helix seven is dependent on the ligand bound. | | <u>Similarities to CD4 in complex with gp120</u>. Analysis of VRC01 in complex with gp120 shows that this complex covers 98% of the CD4 binding site. Insert figure Both the heavy chain and light chain of VRC01 contribute to the contact surfaces of the VRC01 gp120 complex. The focus of the binding is on the heavy chain second complementary-determining region. Over 50% of the surface contact involves the heavy chain second complementary-determining region; this is similar to CD4’s interaction with gp120. Two dominant residues, Phe43 and Arg59, are involved in CD4’s binding to gp120. Of these two residues, only the arginine interaction is mimicked by VRC01. This dominant interaction is between Asp368 of gp120 and Arg59 of the CD4 receptor and between Asp368 of gp120 and Arg71 of VRC01. (Zhou) |
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| <br/> [[Image:MSA.png|center|300px|thumb| MSA [[1xtc]]]] | | <br/> [[Image:MSA.png|center|300px|thumb| MSA [[1xtc]]]] |
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| <u>Other features</u>. 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 | | <u>Other features</u>. VRC01 light chain residues, Tyr28 and Ser30, make contacts with the protein-proximal N-acetyl-glucosamine from the N-linked glycan residue 276 of gp120. While other structures are blocked from binding because glycan shielding, VRC01 takes advantage of the glycan for binding. (Zhou) |
| </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]
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| bcode=3gbg&template=ligands.html&l=1.1] is shown, which can be bound in the beta sheet barrel (as discussed above). This unsaturated fatty acid reduces virulence expression in <i>Vibrio cholerae</i>.
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| </StructureSection> | | </StructureSection> |
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