Journal Article

Ligand binding drives proteolysis of the SmcR master transcription factor and controls quorum sensing-state transitions in Vibrio species

Liang, Biqing, Brockley, Matthew W., Simpson, Chelsea A., Andrew, Finley J., Padgett, Abigail D., Geyman, Logan J., Rasal, Tanmaya A., Mallery, Caleb P., Brown, Laura C., Paczkowski, Jon E., van Kessel, Julia C.

2026

Overview

SmcR family proteins were discovered in the 1990s as central regulators of quorum-sensing gene expression and later discovered to be conserved in all studied Vibrio species. SmcR homologs regulate a wide range of genes involved in pathogenesis, including but not limited to genes involved in biofilm production and toxin secretion. As archetypal members of the broad class of TetR-type transcription factors, each SmcR-type protein has a predicted ligand-binding pocket. However, no native ligand has been identified for these proteins that control their function as regulators. Here, we used SmcR-specific chemical inhibitors to determine that ligand binding drives proteolytic degradation in vivo , providing the first demonstration of SmcR function connected to ligand binding for this historical protein family.

• Publisher: American Society for Microbiology,American Society for Microbiology (ASM)
• Subject: Allosteric properties / Amino acids / Autoinducers / Bacterial Proteins - chemistry / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Bacteriology / Cell density / Editor’s Pick / Gene expression / Gene Expression Regulation, Bacterial / Kinases / Ligands / Microbial Genetics / Microbial Physiology and Genetics / Multidrug resistant organisms / Pathogenesis / Plasmids / Population Dynamics / Protein Binding / Proteins / Proteolysis / Pyrazoles / Quorum Sensing / Quorum Sensing and Regulation / Quorum Sensing and Social Behavior / Quorum Sensing and Virulence / Quorum Sensing in Gram-Negative Bacteria / quorum sensing inhibitors / Quorum Sensing Mechanisms / Quorum Sensing Networks / Quorum Sensing Regulatory Networks / Quorum Sensing Signal Molecules / Regulatory Networks / Research Article / SmcR / Structure-function relationships / Sulfonamides - pharmacology / thiophenesulfonamides / Trans-Activators - genetics / Trans-Activators - metabolism / Transcription factors / Transcription Factors - chemistry / Transcription Factors - genetics / Transcription Factors - metabolism / Variance analysis / Vibrio / Vibrio - drug effects / Vibrio - genetics / Vibrio - metabolism / Vibrio - physiology / Vibrio parahaemolyticus - drug effects / Vibrio parahaemolyticus - genetics / Vibrio vulnificus / Vibrio vulnificus - drug effects / Vibrio vulnificus - genetics / Vibrio vulnificus - metabolism / Vibrio vulnificus - physiology / Virulence