A structural genomics approach to the study of quorum sensing: Crystal structures of three LuxS orthologs

Background: Quorum sensing is the mechanism by which bacteria control gene expression in response to cell density. Two major quorum-sensing systems have been identified, system 1 and system 2, each with a characteristic signaling molecule (autoinducer-1, or Al-1, in the case of system 1, and Al-2 in system 2). The luxS gene is required for the Al-2 system of quorum sensing. LuxS and Al-2 have been described in both Gram-negative and Gram-positive bacterial species and have been shown to be involved in the expression of virulence genes in several pathogens. Results: The structure of the LuxS protein from three different bacterial species with resolutions ranging from 1.8 Angstrom to 2.4 Angstrom has been solved using an X-ray crystallographic structural genomics approach. The structure of LuxS reported here is seen to have a new alpha-beta fold. In all structures, an equivalent homodimer is observed. A metal ion identified as zinc was seen bound to a Cys-His-His triad. Methionine was found bound to the protein near the metal and at the dimer interface. Conclusions: These structures provide support for a hypothesis that explains the in vivo action of LuxS. Specifically, acting as a homodimer, the protein binds a methionine analog, S-ribosylhomocysteine (SRH). The zinc atom is in position to cleave the ribose ring in a step along the synthesis pathway of Al-2.