Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Campylobacter jejuni, a gram-negative bacterial pathogen causing gastroenteritis in humans, the CmeR regulatory protein controls transcription of the multidrug transporter gene operon cmeABC. CmeR belongs to the TetR family of transcriptional regulators. The 210-residue CmeR consists of two functional motifs: an N-terminal DNA-binding domain and a C-terminal ligand-binding domain. It is predicted that the DNA-binding domain interacts directly with target promoters, while the C-terminal motif interacts with inducing ligands (such as bile salts). As an initial step towards confirming this structural model, recombinant CmeR protein containing a 6 x His tag at the N-terminus was crystallized. Crystals of ligand-free CmeR belonged to space group P2(1)2(1)2, with unit-cell parameters a = 37.4, b = 57.6, c = 93.3 A. Diffraction was observed to at least 2.2 A at 100 K. Analysis of the detailed CmeR structure is currently in progress.
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PMID:Preliminary structural studies of the transcriptional regulator CmeR from Campylobacter jejuni. 1718 70

Vibrio parahaemolyticus is a Gram-negative pathogen that causes food-borne gastroenteritis. A major virulence determinant of the organism is a type III secretion system (T3SS2) encoded on a pathogenicity island, Vp-PAI. Vp-PAI gene expression is regulated by two transcriptional regulators, VtrA and VtrB, whose N-terminal regions share homology with an OmpR-family DNA-binding domain. VtrA activates the gene expression of VtrB, which in turn activates Vp-PAI gene expression; however, the mechanism of this transcriptional activation by VtrA is not well understood. In this study, we determined that VtrA is a membrane protein with a transmembrane (TM) domain, which was required for its transcriptional regulatory activity. Although the N-terminal region of VtrA alone is insufficient for its transcriptional regulatory activity, forced oligomerization using the leucine-zipper dimerization domain of yeast GCN4 conferred transcriptional regulatory activity and a greater affinity for the promoter region of vtrB. A ToxR-based assay demonstrated that VtrA oligomerizes in vivo. We also showed that bile, a host-derived activator of VtrA, induces the oligomerization of VtrA, which requires the C-terminal domain. The promoter region of vtrB contained repetitive T-rich DNA elements, which are important for vtrB transcriptional activation and are conserved among T3SS2-possessing Vibrio species. These findings propose that VtrA is active as oligomers, which may facilitate its N-terminus binding the target DNA, thus enhancing its transcriptional regulatory activity.
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PMID:Vibrio parahaemolyticus VtrA is a membrane-bound regulator and is activated via oligomerization. 2914 70