6UGL

Vibrio cholerae quorum-sensing receptor VqmA bound to its autoinducer ligand DPO

Summary for 6UGL

• Entry DOI: 10.2210/pdb6ugl/pdb
• Descriptor: Helix-turn-helix transcriptional regulator, 3,5-dimethylpyrazin-2(1H)-one (3 entities in total)
• Functional Keywords: transcriptional activator protein of quorum sensing genes, 3, 5-dimethylpyrazin-2-ol (dpo), transcription
• Biological source: Vibrio cholerae O1 str. 2010EL-1786
• Total number of polymer chains: 2
• Total formula weight: 55357.58

Authors

Paczkowski, J.E.,Huang, X.,Jeffrey, P.D. (deposition date: 2019-09-26, release date: 2020-01-29, Last modification date: 2025-11-19)

Primary citation

Huang, X.,Duddy, O.P.,Silpe, J.E.,Paczkowski, J.E.,Cong, J.,Henke, B.R.,Bassler, B.L.
Mechanism underlying autoinducer recognition in theVibrio choleraeDPO-VqmA quorum-sensing pathway.
J.Biol.Chem., 295:2916-2931, 2020

PubMed Abstract: Quorum sensing is a bacterial communication process whereby bacteria produce, release, and detect extracellular signaling molecules called autoinducers to coordinate collective behaviors. In the pathogen , the quorum-sensing autoinducer 3,5-dimethyl-pyrazin-2-ol (DPO) binds the receptor and transcription factor VqmA. The DPO-VqmA complex activates transcription of , encoding the VqmR small RNA, which represses genes required for biofilm formation and virulence factor production. Here, we show that VqmA is soluble and properly folded and activates basal-level transcription of its target in the absence of DPO. VqmA transcriptional activity is increased in response to increasing concentrations of DPO, allowing VqmA to drive the quorum-sensing transition at high cell densities. We solved the DPO-VqmA crystal structure to 2.0 Å resolution and compared it with existing structures to understand the conformational changes VqmA undergoes upon DNA binding. Analysis of DPO analogs showed that a hydroxyl or carbonyl group at the 2'-position is critical for binding to VqmA. The proposed DPO precursor, a linear molecule, -alanyl-aminoacetone (Ala-AA), also bound and activated VqmA. Results from site-directed mutagenesis and competitive ligand-binding analyses revealed that DPO and Ala-AA occupy the same binding site. In summary, our structure-function analysis identifies key features required for VqmA activation and DNA binding and establishes that, whereas VqmA binds two different ligands, VqmA does not require a bound ligand for folding or basal transcriptional activity. However, bound ligand is required for maximal activity.

PubMed: 31964715
DOI: 10.1074/jbc.RA119.012104

Experimental method

X-RAY DIFFRACTION (2.03 Å)