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Research Themes Cell biology

Quorum Sensing: E. coli Gets Involved

SBKB [doi:10.1038/sbkb.2014.213]
Featured Article - August 2014
Short description: The crystal structure of E. coli SdiA provides insights into substrate selectivity and oxidation-dependent regulation.

Structure of the SdiA dimer, in ribbon and surface representations, showing the ligand-binding domain on top and the DNA-binding domain at the bottom. Figure courtesy of Kyeong Kyu Kim.

Quorum sensing is a bacterial regulatory mechanism that modulates transcription once a threshold cell concentration is reached, allowing the selective expression of genes required for growth in high cell density conditions. Quorum sensing relies on enzymes producing a small molecule and its cognate receptor, usually orthologs of Vibrio fischeri LuxI and LuxR, respectively. Each LuxI homolog synthesizes an acyl-homoserine lactone (acyl-HSL), which binds to and activates the transcription factor LuxR. Acyl-HSLs vary in the length and structure of the acyl side chain among species.

With regard to quorum sensing systems, Escherichia coli is an interesting exception, as it possesses the LuxR homolog SdiA but lacks a LuxI homolog. E. coli SdiA binds a variety of acyl-HSLs and induces transcription, suggesting that it may respond to signals produced by other bacterial species. Indole also activates gene expression in an SdiA-dependent manner, indicating the potential of SdiA to respond to endogenous signals. SdiA is involved in virulence factor expression of both enterohaemorrhagic E. coli and Salmonella typhimurium and is thus of interest as a potential drug target.

To understand SdiA's substrate specificity and function, Hwang, Kim and colleagues solved the crystal structure of full-length SdiA from E. coli (PDB 4LFU and 4LGW). Like other known LuxR homologs, SdiA forms a symmetrical dimer and each SdiA monomer has an N-terminal ligand-binding domain and a C-terminal DNA-binding domain. While the domain structure is conserved overall, their relative orientation differs among species. The ligand-binding pocket of SdiA is much larger than those in other LuxR homologs, which would explain its broad signal specificity. Still, other structural features of the binding pocket and biochemical assays reveal that SdiA binds most strongly to octanoyl-HSL.

SdiA dimerization is dependent on formation of an intersubunit disulfide bond between Cys232 residues in the DNA-binding domains and can be enhanced by the presence of H2O2, suggesting that the cellular oxidative state could affect SdiA-dependent gene regulation. Indeed, binding of SdiA to a promoter is reduced in the presence of H2O2. The addition of acyl-HSLs does not enhance the affinity of SdiA for its DNA target, but seems to increase the protein's thermal stability.

The study adds an interesting new twist to E. coli's quorum-sensing regulation. Further work will be needed to understand the role of oxidation in activating SdiA targets.

Claudia Lupp

References

  1. T. Kim et al. Structural insights into the molecular mechanism of Escherichia coli SdiA, a quorum-sensing receptor.
    Acta Crystallogr D Biol Crystallogr. 70, 694-707 (2014). doi:10.1107/S1399004713032355

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